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IEEE JOURNAL OF DIPILIH Forum di QUANTUM ELECTRONICS, VOL. 5, NO. 5, NO. 4, JULY/AUGUST 1999 4, Juli / Agustus 1999 1143 1143 Clinical Optical Tomography and NIR Spectroscopy Optical Tomography klinis dan NIR Spektroskopi for Breast Cancer Detection untuk Breast Cancer Detection SB Colak, MB van der Mark, GW't Hooft, JH Hoogenraad, ES van der Linden, and FA Kuijpers SB Colak, MB van der Mark, GW't Hooft, JH Hoogenraad, ES van der Linden, dan FA Kuijpers (Invited Paper) (Diundang Paper) Abstract The results of the first set of clinical trials with the Abstrak-Hasil pertama uji klinis dengan Philips optical mammography prototype system are summarized. Philips optik sistem prototipe mamografi diringkas. This optical mammo prototype is designed to image the interior Prototipe mammo optik ini dirancang untuk gambar interior of the female breast with the help of near-infrared (NIR) laser dari payudara wanita dengan bantuan dekat-inframerah (NIR) laser light transmission measurements. transmisi cahaya pengukuran. This study is expected to lead Studi ini diharapkan untuk memimpin to optical tomography systems for breast cancer detection. untuk sistem tomografi optik untuk deteksi kanker payudara. This Ini paper presents information on the design of the optical mammo menyajikan informasi mengenai desain optik mammo system, the clinical measurements and the imaging results from sistem pengukuran klinis dan hasil pencitraan dari an initial group of ten patients, and discussions about ongoing kelompok awal sepuluh pasien, dan diskusi tentang berkelanjutan research on optical tomography. penelitian tentang tomografi optik. Index Terms Biological tissues, biomedical infrared imaging, Index Syarat-Biologi jaringan, biomedis inframerah imaging, image reconstruction, medical diagnosis, optical spectroscopy, gambar rekonstruksi, diagnosa medis, optik spektroskopi, optical tomography. optik tomography. I. I I. Aku NTRODUCTION ENDAHULUAN BB REAST TUMOR is the leading form of cancer in the REAST TUMOR adalah bentuk kanker terkemuka di female human [1]. perempuan manusia [1]. In contrast to this, it is also one of the Berbeda dengan ini, juga merupakan salah satu dari most treatable forms of cancer, if it can be diagnosed early. sebagian besar jenis kanker dapat disembuhkan, jika dapat didiagnosa dini. The growth rate of breast cancer is exponential with a doubling Tingkat pertumbuhan kanker payudara adalah eksponensial dengan dua kali lipat time of about three months. waktu sekitar tiga bulan. Most primary cancers of breast are Kebanyakan kanker payudara primer adalah

detected by the patients themselves when the average size is terdeteksi oleh pasien sendiri ketika ukuran rata-rata about 2.5 cm. sekitar 2,5 cm. About half of these are already metastatized to Sekitar setengah dari ini sudah metastatized untuk the lymph nodes. kelenjar getah bening. The survival chance of breast cancer drops Kesempatan kelangsungan hidup kanker payudara tetes from a rate of about 95% when the lump is about 0.5 cm size, dari laju sekitar 95% ketika benjolan sekitar 0,5 cm ukuran, to a rate of 75% when the cancer is treated at a size of about ke tingkat 75% bila kanker diperlakukan pada ukuran sekitar 2.5 cm. 2,5 cm. With this information, it is an obvious conclusion that Dengan informasi ini, ini adalah kesimpulan yang jelas bahwa practical and safe diagnosis techniques for this cancer is highly praktis dan aman teknik diagnosa kanker ini sangat desirable. diinginkan. The topic of this report, the medical optical imaging Topik laporan ini, optik pencitraan medis associated with near infrared (NIR) spectroscopy, is expected berhubungan dengan infra merah dekat (NIR) spektroskopi, diharapkan to make routine and frequent mammography practical. untuk membuat mamografi rutin dan sering praktis. At the moment, the reliability of the conventional imaging Pada saat ini, keandalan dari pencitraan konvensional techniques for breast cancer is not perfect. teknik untuk kanker payudara adalah tidak sempurna. The most common Paling umum method of breast imaging, X-Ray mammography, has a high metode pencitraan payudara, XRay mamografi, memiliki tinggi false diagnosis ratio for cancer [2]. diagnosis palsu rasio untuk kanker [2]. The ultrasound imaging Ultrasound imaging techniques can differentiate between solid tumors and cysts. teknik dapat membedakan antara tumor dan kista padat. However, further clinical studies are required to evaluate Namun demikian, studi klinis lebih lanjut diperlukan untuk mengevaluasi this promising technique and increase its specificity. teknik menjanjikan ini dan meningkatkan kekhususan. The Itu magnetic resonance imaging (MRI) provides excellent soft Magnetic Resonance Imaging (MRI) menyediakan lunak baik tissue contrast, but it has to be made more practical for jaringan kontras, tetapi harus dibuat lebih praktis untuk application in breast imaging. aplikasi dalam pencitraan payudara. Both of these latter methods Kedua metode terakhir Manuscript received February 23, 1999; revised June 4, 1999. Naskah diterima 23 Februari 1999; direvisi 4 Juni 1999. SB Colak, MB van der Mark, GW't Hooft, and JH Hoogenraad are SB Colak, MB van der Mark, GW't Hooft, dan JH Hoogenraad adalah with Philips Research Labs, 5656AA Eindhoven, The Netherlands. dengan Philips Research Labs, 5656AA Eindhoven, Belanda. ES van der Linden is with Academic Hospital Maastricht, 6202AZ ES van der Linden adalah dengan Rumah Sakit Akademik Universitas Maastricht, 6202AZ Maastricht, The Netherlands. Maastricht, Belanda.

FA Kuijpers is with Philips Medical Systems, 5680DA Best, The FA Kuijpers adalah dengan Philips Medical Systems, 5680DA Best, The Netherlands. Belanda. Publisher Item Identifier S 1077-260X(99)07525-5. Penerbit Item Identifier S 1077-260X (99) 07525-5. show improved sensitivity if used together with chemical menunjukkan peningkatan sensitivitas jika digunakan bersama dengan kimia contrast agents injected into the patient [2]. agen kontras disuntikkan ke pasien [2]. Another promising method for tissue characterization and Lain metode yang menjanjikan untuk jaringan karakterisasi dan diagnosis is optical imaging [3]. diagnosis optik pencitraan [3]. Due to their advanced enKarena mereka maju en gineering stage, the optical techniques offer a variety of gineering panggung, teknik optik menawarkan berbagai new imaging modalities including time-of-flight methods with modalitas pencitraan baru termasuk waktu-of-penerbangan metode dengan ultra-fast laser pulses, optical coherence tomography, photon laser ultra cepat pulsa, tomografi koherensi optik, foton density wave imaging, among many others. kerapatan gelombang pencitraan, di antara banyak lainnya. Most of these Kebanyakan modalities are currently being studied in a variety of insti- modalitas saat ini sedang belajar di berbagai insti tutes and research groups, including ours. apapun dapat menjadi kelompok dan penelitian, termasuk kita. These are briefly Ini sebentar summarized in the following paragraphs. dirangkum dalam paragraf berikut. Optical radiation has been first used in diaphanoscopy in Radiasi optik telah digunakan di diaphanoscopy pertama di 1929 to image breast tumors by shadowing effect [4]. 1929 sampai gambar payudara tumor oleh efek bayangan [4]. In Di diaphonoscopy, the difference in the absorption coefficient of diaphonoscopy, perbedaan dalam koefisien penyerapan various tissues enables the detection of inhomogeneities in the berbagai jaringan memungkinkan deteksi di inhomogeneities breast. dada. The areas of dense tumor or hematoma look darker, Bidang padat tumor atau hematom terlihat lebih gelap, while the pockets of cyst look clearer as compared to the sedangkan kantong kista terlihat lebih jelas dibandingkan dengan surrounding tissues. jaringan sekitarnya. Diaphanography, which is based on this Diaphanography, yang didasarkan pada basic idea, has been tested in several hospitals in the 1980's, Ide dasar, telah diuji di beberapa rumah sakit di tahun 1980-an, as preliminary examination tool before a biopsy. sebagai alat pemeriksaan pendahuluan sebelum biopsi. As has been Seperti telah summarized before [5], the breast cancer detection rate is about diringkas sebelum [5], kanker payudara tingkat deteksi adalah 30% with the conventional diaphanography. 30% dengan diaphanography konvensional. In the 1990's, we have seen many other new modalities of Pada tahun 1990, kami telah melihat banyak modalitas baru dari medical optical imaging. optik pencitraan medis. This has been primarily due to the Ini telah terutama karena

strong advancements in near-infrared (NIR) laser and detector kemajuan kuat di dekatinframerah (NIR) laser dan detektor technologies, suitable for biological tissue characterization. teknologi, cocok untuk karakterisasi jaringan biologis. For example, an advanced version of diaphonoscopy has Sebagai contoh, sebuah versi lanjutan telah diaphonoscopy been studied with scanned (fiber) laser light [6]. telah dipelajari dengan scan (serat) sinar laser [6]. In another Lain investigation, optical measurements have been extended with penyelidikan, pengukuran optik telah diperpanjang dengan light which is modulated at near-gigahertz frequencies, to cahaya yang dimodulasi pada frekuensi di dekat-gigahertz, untuk obtain better contrast and resolution in the images [7]. memperoleh kontras dan resolusi yang lebih baik pada gambar [7]. This Ini approach is under current clinical study [8]. Pendekatan ini berdasarkan studi klinis saat ini [8]. Time resolved Sisa diselesaikan transillumination with short laser pulses has been studied for transillumination dengan pulsa laser pendek telah dipelajari untuk the extraction of different tissue parameters [9]. ekstraksi parameter jaringan yang berbeda [9]. Such short Pendek seperti pulse methods have also been applied in actual mammographic metode denyut nadi juga telah diterapkan di mammographic aktual imaging trials with volunteer patients [10]. pencitraan pengadilan dengan relawan pasien [10]. During the recent Selama baru years, there has also been a good amount of breast tissue tahun, ada juga yang baik jumlah jaringan payudara spectroscopy done on volunteers [11]. Spektroskopi dilakukan pada sukarelawan [11]. These studies have Studi tersebut telah further resulted in mammographic imaging systems which lebih lanjut mengakibatkan sistem pencitraan yang mammographic are also under current clinical trials [12]. juga dalam uji klinis saat ini [12]. In some cases, Dalam beberapa kasus, medical contrast agents have also been tried to evaluate their agen kontras medis juga telah mencoba untuk mengevaluasi use in optical imaging [13]. digunakan dalam pencitraan optik [13]. There are actually efforts to Sebenarnya ada upaya untuk commercialize some of the optical imaging methods described mengkomersialkan beberapa pencitraan optik metode yang dijelaskan above [14]. di atas [14]. Although, in our research group, we have also investigated Meskipun, dalam kelompok riset kami, kami juga meneliti the use of short laser pulses [15] and photon density waves, penggunaan laser pendek pulsa [15] dan kerapatan foton gelombang, 1077260X/99$10.00 1999 IEEE 1077-260X/99 $ 10,00 1999 IEEE Page 2 Page 2 1144 1144 IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS, VOL. IEEE JOURNAL OF DIPILIH Forum di QUANTUM ELECTRONICS, VOL. 5, NO. 5, NO. 4, JULY/AUGUST 1999 4, Juli / Agustus 1999

[16], [17], in medical imaging, we have decided to do our [16], [17], dalam pencitraan medis, kami telah memutuskan untuk melakukan yang initial clinical trials with continuous wave (CW) laser sources uji klinis awal dengan gelombang kontinu (CW) laser sumber [18]. [18]. Our method uses many source and detector fiber probes Metode kami menggunakan banyak sumber dan detektor serat probe attached solidly on the inner surface of a cup which is placed terpasang kokoh pada permukaan bagian dalam sebuah cangkir yang ditempatkan around the patients breast. di sekitar payudara pasien. This approach provides a more Pendekatan ini memberikan tampilan yang lebih practical and reliable hardware setup which is suitable for praktis dan dapat diandalkan setup hardware yang cocok untuk clinical trials. uji klinis. We have actually built a clinical prototype Kita sebenarnya telah membangun sebuah prototipe klinis for optical mammography and have been testing it clinically untuk optik mamografi dan telah mengujinya secara klinis during the past couple of years. selama beberapa tahun. We have also reported some of Kami juga telah melaporkan beberapa our initial results previously [19], [20]. hasil awal kami sebelumnya [19], [20]. In this paper, we would Dalam makalah ini, kami akan like to present a more complete description of our experiments seperti untuk menyajikan gambaran yang lebih lengkap eksperimen kami and results and also discuss future possibilities of research dan hasil dan juga mendiskusikan kemungkinan masa depan penelitian with this approach. dengan pendekatan ini. II. II. T T ISSUE ISSUE OO PTICS PTICS In this section, we will give a brief review on the basic Dalam bagian ini, kami akan memberikan ulasan singkat mengenai dasar components of healthy and diseased tissue, and their main komponen jaringan sehat dan sakit, dan utama mereka optical properties. optiknya. Biological tissue is made up of a large Jaringan biologis terdiri dari besar number of molecules consisting of primarily carbon, hydrogen, jumlah molekul terutama terdiri dari karbon, hidrogen, oxygen, and nitrogen atoms [21], [22]. oksigen, dan nitrogen atom [21], [22]. These atoms are bound Atom ini terikat into a vast variety of small and large molecules, up to menjadi luas berbagai molekul besar dan kecil, hingga times kali the weight of an H atom. berat atom H. This large variety of molecules form Besar ini berbagai bentuk molekul the cells of a biological organizm. sel-sel biologis organizm. Cells contain 70%80% Sel mengandung 70% -80% water, and 1020% of lipids, fatty molecules which form the air, dan 10-20% lemak, molekul lemak yang membentuk cell membranes. membran sel. The interior of cells can contain particles Interior sel dapat mengandung partikel

and macromolecules of highly varied shapes and dimensions dan makromolekul yang sangat bervariasi bentuk dan dimensi ranging from 100 s of angstroms to 100 s of micrometers. mulai dari 100 s dari angstrom sampai 100 s dari mikrometer. These include large molecules such as proteins, amino acids, Ini termasuk molekul-molekul besar seperti protein, asam amino, nucleic acids (DNA), and polysaccharides. asam nukleat (DNA), dan polisakarida. Cells, depending Sel, tergantung on the different organs of a human, can have many different pada organ-organ yang berbeda manusia, dapat mempunyai banyak berbeda shapes and sizes varying from 10100 m. bentuk dan ukuran yang bervariasi 10-100 m. Due to the refractive index variations in the length scales Karena variasi indeks bias dalam skala panjang described above, the propagation of light in tissue has a diffuse dijelaskan di atas, propagasi cahaya dalam jaringan memiliki difusi character. karakter. Structural fibers and nuclei Struktural serat dan nuklei 1.45) in -1,45) Di a background of cytoplasm latar belakang sitoplasma and extracellular dan ekstraselular fluid fluida are the origin for the main part of the adalah asal untuk bagian utama dari index variations [23]. indeks variasi [23]. Light absorption occurs primarily on Cahaya penyerapan terjadi terutama pada discrete portions of the cells known as chromophores, such diskrit bagian dari sel-sel yang dikenal sebagai chromophores, seperti as chromatin, cytochrome, haemoglobin and myoglobin. sebagai kromatin, sitokrom, hemoglobin dan mioglobin. The Itu three last pigments change their optical characteristics as a tiga pigmen terakhir mengubah karakteristik optik sebagai function of the metabolism, whether the pigment is oxidized or fungsi metabolisme, apakah pigmen teroksidasi atau reduced [5]. dikurangi [5]. Obviously living tissue is also a dynamic system. Jelas jaringan hidup juga merupakan sistem dinamik. It changes properties and shape with, again, highly varying It perubahan sifat dan bentuk dengan, sekali lagi, sangat bervariasi time scales. skala waktu. For example, heart beat, with about 1/80 of a Sebagai contoh, jantung berdetak, dengan sekitar 1 / 80 dari sebuah minute of period, changes the shape of the veins, the organs periode menit, perubahan bentuk pembuluh darah, organ-organ and the oxygenation state of many molecules contained in dan keadaan oksigenasi banyak molekul yang terkandung dalam them. mereka. There are many molecules in motion in the blood stream, Ada banyak molekul dalam gerakan dalam aliran darah, and they result in Doppler broadening of the scattered light dan mereka menghasilkan Doppler perluasan dari cahaya yang tersebar with time scales in the order of sub milliseconds. dengan skala waktu dalam urutan sub milidetik. Due to all Karena semua these reasons, it is very difficult to obtain clear optical images alasan ini, sangat sulit untuk mendapatkan gambar yang jelas optik

of the interior of the biological tissue by direct methods. dari bagian dalam jaringan biologis metode langsung. Furthermore, because of the same effects, the biological tissue Lebih jauh lagi, karena efek yang sama, jaringan biologis usually responds to optical excitation in a very indistinct way, biasanya merespons eksitasi optik dalam cara yang sangat tidak jelas, making the spectroscopic identification of different tissue types membuat identifikasi spektroskopi jenis jaringan yang berbeda difficult. sulit. Despite these difficulties, due to the expected safety and Meskipun kesulitan-kesulitan ini, karena diharapkan keselamatan dan easiness of optical imaging methods, there have been numer- optik pencitraan kemudahan metode, ada numer ous studies to determine the optical properties of tissue. ous studi untuk menentukan sifat optik jaringan. To Untuk Fig. Gambar. 1. 1. Relative transmission of the most relevant absorbing compounds in Relatif transmisi yang paling relevan dalam menyerap senyawa biological tissues in the visible and NIR region (adapted from [24]). biologis jaringan di wilayah terlihat dan NIR (diadaptasi dari [24]). Water Air (OH), fat (CH) and hemoglobin (Hb,HbO) are the most important absorbers (OH), lemak (CH) dan hemoglobin (Hb, HBO) adalah yang paling penting absorbers in tissue. dalam jaringan. The vertical lines indicate the laser wavelengths used in our study Garis vertikal menunjukkan panjang gelombang laser yang digunakan dalam penelitian presented here. disajikan di sini. Fig. Gambar. 2. 2. Pathological slide for an intraductal carcinoma [27], emphasizing the Patologis slide untuk intraductal karsinoma [27], yang menekankan high heterogeneity of the breast tissue. heterogenitas yang tinggi dari jaringan payudara. The malignant cells are confined to Sel-sel yang ganas terbatas pada the ducts (1). saluran (1). There is a region of degenerating (necrotic) cells (2). Ada wilayah memburuk (nekrotik) sel-sel (2). Normal Normal lobules (3), fibrous stroma (4) and fat (5) regions are also shown. lobulus (3), stroma fibrosa (4) dan lemak (5) daerah juga ditampilkan. Sketch in Sketsa the inset shows the vascularization of the cancerous region. insetnya menunjukkan vascularization dari daerah kanker. Due to this and Karena ini dan also associated hemorrhages, these regions result in higher optical absorption juga berhubungan perdarahan, daerah ini menghasilkan penyerapan optik yang lebih tinggi near Hb bands indicated in Fig. Hb dekat band ditunjukkan pada Gambar. 1. 1. summarize some of these, we first give the relative trans- merangkum beberapa di antaranya, pertama-tama kita memberikan relatif trans mission spectra of the most relevant absorbing compounds in spektrum misi yang paling relevan dalam menyerap senyawa tissues in Fig. jaringan dalam Gambar. 1. 1. Water, fat and hemoglobin are most important Air, lemak dan hemoglobin adalah yang paling penting absorbers in tissue [24]. absorber dalam jaringan [24]. This set of curves has sufficient detail Set kurva ini telah cukup detail to label the major features in a full transmission spectra of in untuk label fitur-fitur utama dalam transmisi spektrum penuh dalam vivo breast, as given previously [24]. vivo payudara, seperti yang diberikan sebelumnya [24]. We also observe that, Kami juga mengamati bahwa,

there is a window from 650 to 900 nm, where the lowest ada jendela 650-900 nm, di mana terendah percentage of light is absorbed. persentase cahaya yang diserap. From these one expects that, it Dari seorang pun mengharapkan bahwa, hal should still be possible to identify the weak absorption peaks seharusnya masih dapat dibuat untuk mengidentifikasi puncak penyerapan lemah coming from haemoglobin, fat and water. berasal dari hemoglobin, lemak dan air. For example, one Sebagai contoh, satu can deduce that a wavelength at 780 nm should show the dapat menyimpulkan bahwa panjang gelombang pada 780 nm harus menunjukkan strongly blood perfused parts of the breast as a shadow as perfused darah kuat bagian payudara sebagai bayangan sebagai compared to other tissues containing more water, for example. dibandingkan dengan jaringan lain yang mengandung lebih banyak air, misalnya. In cancer, the regular cellular growth cycle of cells changes Pada kanker, sel biasa siklus pertumbuhan sel perubahan due to the mutations in the DNA, resulting in variations in karena mutasi pada DNA, menyebabkan variasi dalam the cell cycle times [25]. siklus sel kali [25]. Most carcinomas in the breast arise Kebanyakan karsinoma pada payudara timbul in the epithelial lining of the milk glands and ducts [26]. dalam lapisan epitel kelenjar susu dan saluran [26]. Different components of breast cancer and surrounding tissues Komponen yang berbeda kanker payudara dan jaringan sekitarnya are shown in the pathological slide in Fig. akan ditampilkan dalam slide patologis dalam Gambar. 2. 2. In the avascular Dalam avascular phase the initial clump of malignant cells can remain as a rumpun fase awal dari sel-sel ganas dapat tetap sebagai Page 3 Halaman 3 COLAK et al. : CLINICAL OPTICAL TOMOGRAPHY AND NIR SPECTROSCOPY FOR BREAST CANCER DETECTION COLAK et al.: KLINIS OPTIK spektroskopi NIR tomography DAN UNTUK KANKER PAYUDARA DETECTION 1145 1145 Fig. Gambar. 3. 3. The optical mammo prototype system. Mammo optik sistem prototipe. The arrow near the cup area Panah di dekat daerah cangkir toward the computer monitor indicates the reference point where the images ke arah monitor komputer menunjukkan titik acuan di mana gambar discussed in the text are registered. dibahas dalam teks terdaftar. harmless in situ carcinoma for many years at a size of about 1 in situ karsinoma tidak berbahaya selama bertahun-tahun di ukuran sekitar 1 mm. mm. Further growth requires vascularization, where the nearby Vascularization membutuhkan pertumbuhan lebih lanjut, di mana di dekatnya blood vessels send out capillaries into the tumor. pembuluh darah kapiler mengirimkan ke tumor. This leads Ini mengarah to a vascularized lump with irregular and diffuse boundaries ke vascularized benjolan dengan batas-batas yang tidak teratur dan baur [28] as shown schematically in Fig. [28] seperti yang ditunjukkan secara skematik pada Gambar. 2 as inset. 2 sebagai inset. Due to this Karena ini

rapid vascularization, tumors have high internal pressure and vascularization cepat, tumor memiliki tekanan internal yang tinggi dan result in hemorrhages [29]. mengakibatkan perdarahan [29]. These regions are irrigated heavily Irigasi wilayah ini sangat in hypoxic blood, showing up as highly absorbing regions in di hipoksia darah, muncul sebagai sangat menyerap daerah di optical transmission. transmisi optik. In order to utilize the optical techniques in diagnosis ef- Dalam rangka untuk menggunakan teknik-teknik optik diagnosis ef fectively, we must characterize the biological tissue with its fectively, kita harus ciri jaringan biologis dengan most important parameters. parameter yang paling penting. Spectroscopic analysis of such Analisis spektroskopi seperti parameters can lead to differentiation of the phenomena such parameter dapat menyebabkan diferensiasi dari fenomena tersebut as vascularization in cancer core as well as the molecular sebagai inti kanker vascularization serta molekuler differences in the same region, leading to the detection and perbedaan-perbedaan di daerah yang sama, yang mengarah ke deteksi dan assessment of cancer. penilaian kanker. Such spectral differences have been Seperti telah perbedaan spektral reported in measurements for the absorption, fluorescence, dilaporkan dalam pengukuran untuk penyerapan, fluoresensi, light diffusion, Raman scattering, etc. [30]. cahaya difusi, hamburan Raman, dll [30]. It should be Harus realized, however, that the cancerous tissue has a rather menyadari, bagaimanapun, bahwa jaringan kanker telah agak diffusive boundary, and the appearance and the molecular difusif batas, dan penampilan dan molekuler properties of cancerous tissue of various kinds of tumors sifat jaringan kanker berbagai jenis tumor differ greatly. berbeda jauh. Despite this variations, biological tissue has Meskipun variasi ini, memiliki jaringan biologis been characterized mainly by a few parameters depending terutama dicirikan oleh beberapa parameter tergantung on the diffusion properties of the light within it. pada sifat difusi cahaya di dalamnya. Most of Sebagian such collected data are normally presented as absorption, mengumpulkan data seperti itu biasanya disajikan sebagai penyerapan, , and scattering , Dan menyebarkan coefficients, usually given in units of koefisien, biasanya diberikan dalam satuan (1/m) or (1/mm). (1 / m) atau (1/mm). Numerical values of these optical parameters Nilai numerik parameter optik ini within 700900 nm range for breast tissue, which are around dalam rentang 700-900 nm jaringan payudara, yang sekitar 1/mm for 1/mm untuk and 0.05/mm for dan 0.05/mm untuk , have been reported in , Telah dilaporkan previous studies [31][34]. penelitian sebelumnya [31] - [34]. Note that the attenuation constant Perhatikan bahwa pelemahan konstan

values discussed later, are related to these parameters by nilai dibahas kemudian, berkaitan dengan parameter ini dengan III. III. O O PTICAL PTICAL MM AMMO Amunisi PP ROTOTYPE ROTOTYPE In order to be able to do clinical optical imaging for breast Untuk dapat melakukan pencitraan optik klinis payudara cancer we have built an optical mammography prototype kanker kami telah membangun prototipe mamografi optik system. sistem. A photo of this system is shown in Fig. Sebuah foto dari sistem ini ditunjukkan pada Gambar. 3. 3. Its most Paling Fig. Gambar. 4. 4. The close up photo of the cup region of the prototype. Foto yang dekat dari daerah cangkir prototipe. Tips of some Tips dari beberapa of the source and detector fibers are seen within the cup. dari sumber dan detektor serat terlihat dalam cangkir. The red diverging Divergen merah light is from one of the source fibers emitting at around 670 nm. cahaya dari salah satu sumber memancarkan serat sekitar 670 nm. important element is the cup region shown in the following elemen penting adalah wilayah cangkir ditunjukkan pada berikut Fig. Gambar. 4, where the transmission of the breast is measured over 4, di mana transmisi payudara diukur atas a conical surface. permukaan berbentuk kerucut. On the boundary of the cup 255 optical Di batas cangkir optik 255 fibers are mounted that lead to one detector each. serat dipasang yang mengarah ke satu detektor masing-masing. Interleaved, Interleaved, 255 fibers are mounted that can be selected sequentially to 255 serat dipasang yang dapat dipilih secara berurutan untuk receive the light of one of the three continuous-wave diode menerima cahaya dari salah satu dari tiga gelombang kontinu dioda lasers that are operating at different wavelengths in the NIR. laser yang beroperasi pada panjang gelombang yang berbeda di NIR. All detectors measure simultaneously so that one complete Semua detektor mengukur secara simultan sehingga satu lengkap measurement for one wavelength takes less than 2 min. pengukuran untuk satu panjang gelombang memakan waktu kurang dari 2 menit. The Itu conical cup geometry and the CW operation, in our prototype, cangkir berbentuk kerucut geometri dan operasi CW, dalam prototipe kami, were chosen as a result of our conclusions from previous dipilih sebagai hasil dari kesimpulan dari sebelumnya studies with phantoms [16][18]. penelitian dengan hantu [16] - [18]. Although the photo of the cup shown in Fig. Meskipun foto cangkir yang ditunjukkan pada Gambar. 4 indicates 4 menunjukkan that the boundary of the cup is black, most of our clinical bahwa batas cangkir hitam, sebagian besar klinis measurements were done by using a reflecting surface for pengukuran dilakukan dengan menggunakan permukaan untuk mencerminkan

the cup. cangkir. The reasons are as follows. Alasannya adalah sebagai berikut. During our studies we Selama kajian-kajian kami kita found that the main difficulty in reconstructing an image is the menemukan bahwa kesulitan utama dalam membangun kembali gambar adalah influence of the boundary on the observability of small objects pengaruh batas pada benda kecil observability inside the medium. dalam medium. In a continuous-wave (CW) technique, a Dalam gelombang kontinu (CW) teknik, sebuah reflecting boundary enhances the detectibility as compared to meningkatkan batas mencerminkan detectibility dibandingkan dengan a black boundary. batas hitam. However, a reflecting boundary reduces the Namun, mengurangi batas mencerminkan image resolution, but only marginally. resolusi gambar, tetapi hanya sedikit. This medium is the Media ini adalah breast in our case, which has a attenuation constant of about payudara dalam kasus kami, yang memiliki konstanta pelemahan tentang mm. mm. We used a reflecting cup, with an optical Kami menggunakan cangkir mencerminkan, dengan optik coefficient providing an effective loss that is about the same koefisien memberikan kerugian yang efektif adalah sama as the sebagai of average breast, so the resolution is affected very payudara rata-rata, sehingga resolusi sangat dipengaruhi little. kecil. As a result however, the light levels increase. Namun Akibatnya, tingkat cahaya meningkat. Moreover, Terlebih lagi, the system resembles an infinite medium better, resulting in menyerupai sistem media yang tak terbatas lebih baik, sehingga easier and faster computations for the image reconstruction. perhitungan lebih mudah dan lebih cepat untuk gambar rekonstruksi. The transmission spectra and the optical diffusion parame- Spektrum transmisi dan difusi optik parameter ters of the in vivo breast tissue was discussed in the previous Ters dari dalam jaringan payudara vivo telah dibahas di sebelumnya section. bagian. From there and also from the discussion given in the Dari sana dan juga dari diskusi yang diberikan dalam previous paragraph, we know that the attenuation in breast paragraf sebelumnya, kita tahu bahwa pelemahan di payudara tissue in its most transparent region is in the order of 100150 jaringan di wilayah yang paling transparan dalam urutan 100-150 m . m. Of all the methods considered and discussed in the Dari semua metode yang dipertimbangkan dan dibahas dalam introduction, only continuous wave (CW) transillumination pengenalan, hanya gelombang kontinu (CW) transillumination provides the dynamic range of about 4 10 to allow mea- menyediakan dinamis jarak sekitar 4 10 untuk membolehkan mea Page 4 Halaman 4 1146 1146

IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS, VOL. IEEE JOURNAL OF DIPILIH Forum di QUANTUM ELECTRONICS, VOL. 5, NO. 5, NO. 4, JULY/AUGUST 1999 4, Juli / Agustus 1999 Fig. Gambar. 5. 5. The operation of the mechanical switch which is designed to choose Pengoperasian saklar mekanis yang dirancang untuk memilih the laser wavelength for the source fiber set is shown here. panjang gelombang laser untuk sumber serat set yang ditampilkan di sini. This operation is Operasi ini controlled fully automatically by a PC. dikontrol sepenuhnya secara otomatis oleh PC. Fig. Gambar. 6. 6. The results of measurements testing the reproducibility of the me- Hasil pengujian pengukuran reproduktifitas dari saya chanical fiber switch. serat chanical saklar. The error is within 5 mV, which corresponds to about Kesalahan adalah dalam waktu 5 mV, yang sesuai dengan tentang 0.1% of the full scale signal of about 5 V shown in the plotted results. 0,1% dari sinyal skala penuh sekitar 5 V ditampilkan dalam hasil diplot. surements over all source detector distances of 5130 mm for surements atas semua detektor sumber jarak 5-130 mm untuk the cup region of our prototype. daerah cangkir prototipe kami. Therefore, we have chosen Oleh karena itu, kita telah memilih to work with CW diode lasers operating in the near infrared. untuk bekerja dengan dioda laser CW beroperasi di dekat inframerah. For the main portion of our clinical trials, the wavelengths we Untuk bagian utama kami uji klinis, panjang gelombang kami have chosen are 660, 780, and 920 nm. telah memilih adalah 660, 780, dan 920 nm. However, during these Namun, selama ini trials, we have noted too much noise with the measurements cobaan, kami telah mencatat terlalu berisik dengan pengukuran with the laser at the longest wavelength of 920 nm due to the dengan laser pada panjang gelombang terpanjang 920 nm karena low transmission of tissue. jaringan transmisi rendah. Therefore, we decided to switch Oleh karena itu, kami memutuskan untuk beralih this laser with a new laser operating at a wavelength of 870 laser ini dengan laser baru beroperasi pada panjang gelombang 870 nm to decrease some of the noise in these measurements. nm untuk menurunkan beberapa kebisingan dalam pengukuran ini. During the measurements, the laser wavelengths are selected Selama pengukuran, panjang gelombang laser dipilih sequentially and automatically with a mechanical switch as secara berurutan dan secara otomatis dengan saklar mekanis shown in Fig. ditunjukkan pada Gambar. 5. 5. Actually, the only mechanical selection Sebenarnya, satu-satunya pilihan mekanis involved in our measurements is this laser source switching terlibat dalam pengukuran adalah sumber laser ini switching to the source fibers. ke sumber serat. The reproducibility of the switch was The reproduktifitas dari saklar ini tested by measuring the coupled output power to a reference diuji dengan mengukur output digabungkan kekuatan untuk referensi detector. detektor. The results of this test are shown in Fig. Hasil tes ini diperlihatkan pada Gambar. 6. 6. As Sebagai seen the error introduced into the measurements due to this melihat kesalahan diperkenalkan ke dalam pengukuran karena ini

mechanical switch is about 0.1%. saklar mekanik sekitar 0,1%. The power output from the Daya output dari lasers are about 50 mW. laser sekitar 50 mW. Some of this power gets lost in the Beberapa kekuatan ini akan hilang dalam fibers and their connectors before reaching the cup. serat dan konektor sebelum mencapai cangkir. Fig. Gambar. 7. 7. The measurement system of the cup area showing the laser light Sistem pengukuran daerah cangkir menunjukkan sinar laser injection, collection and the detection system. injeksi, koleksi dan sistem deteksi. Fig. Gambar. 8. 8. The histogram of the detector dark noise measured from the prototype Histogram dari gelap detektor suara diukur dari prototipe system. sistem. For the load resistor the mV figures translate to fW on the Untuk resistor beban menerjemahkan angka-angka yang mV untuk FW di xx axis. sumbu. The measurement system related to the cup area is schemat- Sistem pengukuran yang berkaitan dengan daerah cangkir schemat ically shown in Fig. ically ditunjukkan pada Gambar. 7. 7. The laser light, which is introduced Sinar laser, yang diperkenalkan from the source fiber, diffuses around in the cup medium dari sumber serat, berdifusi di dalam cangkir media containing inhomogeneities and some of this light exits at the berisi inhomogeneities dan beberapa cahaya ini keluar pada detector fiber. detektor serat. The fibers attached to the cup area are plastic Serat yang melekat pada kawasan cangkir plastik and have a size of about a mm in diameter. dan memiliki ukuran tentang mm diameter. The efficiency Efisiensi of the pin photo diode, at the other end of this fiber, is about dari dioda foto pin, di ujung lain dari serat ini, adalah tentang 0.6 A/W. 0,6 A / W. Although it is not shown explicitly, a number of Meskipun tidak ditampilkan secara eksplisit, sejumlah load resistors present in the circuitry allows a large dynamic beban resistor hadir di sirkuit memungkinkan dinamis besar range by automatic selection of the appropriate load resistor. Rentang oleh seleksi otomatis resistor beban yang sesuai. This selection is achieved by special solenoid switches. Pilihan ini dicapai dengan switch solenoida khusus. As a Sebagai result, the detection system has a dynamic range of 4 10 Akibatnya, sistem deteksi memiliki jangkauan dinamis 4 10 and an NEP of 25 fW. dan NEP 25 FW. The dark noise from this system was Kebisingan gelap dari sistem ini adalah measured and the results are plotted in Fig. diukur dan hasilnya diplot pada Gambar. 8. 8. As seen, this Seperti yang terlihat, ini Page 5 Halaman 5 COLAK et al. : CLINICAL OPTICAL TOMOGRAPHY AND NIR SPECTROSCOPY FOR BREAST CANCER DETECTION COLAK et al.: KLINIS OPTIK spektroskopi NIR tomography DAN UNTUK KANKER PAYUDARA DETECTION 1147 1147

Fig. Gambar. 9. 9. The prototype cup and the positioning of the patient's breast within Prototipe cangkir dan posisi dada pasien dalam it during the measurement procedures. selama prosedur pengukuran. dark noise and the fluctuations due to the mechanical fiber kebisingan gelap dan fluktuasi karena serat mekanis switch discussed above, are both well under the acceptable beralih dibahas di atas, keduanya baik di bawah dapat diterima measurement range of the detector system. rentang pengukuran sistem detektor. Furthermore, it Selain itu, should be stated that the bit noise due to AD conversion is harus dinyatakan bahwa sedikit kebisingan akibat konversi AD also less than a millivolt. juga kurang dari millivolt. The drift in the measurement system, Arus di sistem pengukuran, due to the detector and source stability during a period of 30 karena detektor dan sumber stabilitas selama periode 30 min, is about 5 mV, or 0.2%. min, adalah sekitar 5 mV, atau 0,2%. Note that, since our data is based Perhatikan bahwa, karena data kami didasarkan to a reference measurement, the constant losses, such as the untuk referensi pengukuran, kerugian yang terus-menerus, seperti ones due to fiber input and propagation, is not expected to yang disebabkan oleh serat masukan dan propagasi, tidak diharapkan untuk introduce errors in our imaging. memperkenalkan kesalahan dalam pencitraan kita. IV. IV. E E XPERIMENTS XPERIMENTS In a normal measuring sequence, the prototype cup is Dalam urutan mengukur normal, cangkir prototipe filled with a matching fluid. diisi dengan cairan yang serasi. The subject has to lie down Topik ini telah untuk berbaring on the machine and let one of her breasts hang freely in pada mesin dan membiarkan salah satu payudaranya menggantung bebas di the cup containing the fluid. cangkir berisi cairan. The cup and the positioning Cangkir dan posisi of the patients breast during the measurements are shown dada pasien selama pengukuran ditampilkan in Fig. pada Gambar. 9. 9. The fluid is specially designed to match the mean Fluida dirancang khusus agar sesuai dengan mean optical properties of the breast. sifat optik payudara. It is kept at around 31 C Hal ini disimpan di sekitar 31 C for comfort. untuk kenyamanan. The main function of this fluid is simply to Fungsi utama cairan ini hanya untuk decrease the unwanted contrast in the transmitted light due mengurangi kontras yang tidak diinginkan dalam cahaya yang ditransmisikan karena to voids that would be present in the absence of this fluid. untuk void yang akan hadir dalam ketiadaan cairan ini. As Sebagai discussed in the next section, this makes the computations for dibahas dalam bagian berikutnya, hal ini membuat perhitungan untuk tomographic image reconstruction more manageable. rekonstruksi citra tomografi lebih mudah dikelola. During a Selama normal measurement, the signal for all detector positions are pengukuran normal, sinyal untuk semua posisi detektor

measured simultaneously, with all source positions addressed diukur secara bersamaan, dengan semua posisi sumber dialamatkan in sequence. berurutan. First, a reference measurement only with the Pertama, pengukuran referensi hanya dengan matching liquid, without the breast, is made and stored for the pencocokan cair, tanpa payudara, dibuat dan disimpan untuk calibration of the sources and detectors at a later step. kalibrasi dari sumber dan detektor pada langkah berikutnya. Then, Kemudian, immediately following the reference measurement, the same segera setelah referensi pengukuran, yang sama set of measurements is performed for one breast and then the set pengukuran dilakukan untuk satu payudara dan kemudian other breast. payudara lain. Within each set, all of these are repeated three Dalam setiap rangkaian, semua ini diulang tiga times corresponding to each of the three different wavelengths. kali sesuai dengan masingmasing dari tiga panjang gelombang yang berbeda. This makes a total of nine measurements per patient. Hal ini membuat total sembilan pengukuran per pasien. After the Setelah data collection, the reference measurement is used to calibrate pengumpulan data, referensi pengukuran digunakan untuk kalibrasi the sources and the detectors. sumber dan detektor. Fig. Gambar. 10. 10. Difference in the transmitted test intensity with and without the 10 Perbedaan dalam intensitas tes yang ditransmisikan dengan dan tanpa 10 mm diameter black bead discussed in the text. mm diameter manik hitam yang dibahas dalam teks. The vertical axis on the surface Sumbu vertikal pada permukaan plot on the right is the logarithmic difference intensity, plot di sebelah kanan adalah perbedaan logaritma intensitas, dI dI . . The horizontal axis Sumbu horizontal labeled berlabel " kk represents the fiber ring layers in the cup. "Mewakili cincin serat lapisan dalam cangkir. The other axis labeled Sumbu yang lain diberi label " jj is for the number of detector fiber in a given ring. "Adalah untuk jumlah detektor serat dalam suatu cincin. The transmission Transmisi shadow of the bead appears as the black area centered at bayangan dari manik-manik muncul sebagai daerah hitam berpusat di (k; j) = (7; 15) (k; j) = (7; 15) .. Fig. Gambar. 11. 11. The cup geometry describing the indices for the difference intensity Geometri cangkir indeks untuk menggambarkan perbedaan intensitas plots in Fig. plot pada Gambar. 10. 10. The arrow on the top right corner corresponds to the same Panah di sudut kanan atas sesuai dengan yang sama location in the prototype bed, in Fig. lokasi di tempat tidur prototipe, pada Gambar. 3, labeled as the reference point. 3, dilabeli sebagai titik acuan. In order to be able to test the prototype and determine its Dalam rangka untuk dapat menguji dan menentukan prototipe

limitations due to noise on image forming, we have made a keterbatasan akibat kebisingan pada gambar membentuk, kami telah membuat series of initial experiments with simple phantoms consisting serangkaian percobaan awal dengan hantu sederhana yang terdiri of beads in a matching fluid. manik-manik dalam cairan yang serasi. For this, the matching fluid Untuk ini, fluida yang cocok consisted of 1% intralipid solution in water. terdiri dari 1% intralipid larutan dalam air. The results shown Hasil ditampilkan in Fig. pada Gambar. 10 are for a sapphire bead. 10 adalah untuk manik batu safir. The bead has a 10 mm Manik-manik memiliki 10 mm diameter and is painted black on its surface. diameter dan dicat hitam pada permukaannya. The results Hasil plotted in Fig. diplot pada Gambar. 10 is the light intensity difference between the 10 adalah perbedaan intensitas cahaya antara measurement in the presence of the bead and the reference pengukuran di hadapan manikmanik dan referensi measurement where the bead was removed. pengukuran di mana manik telah dihapus. That is; Yaitu; (1) (1) where di mana is the intensity difference between the measured test adalah intensitas diukur perbedaan antara tes data intensity, data intensitas and the reference intensity, dan referensi intensitas, measured in diukur the absence of the bead. adanya manik-manik. This transmitted light difference, is Cahaya yang ditransmisikan perbedaan ini, adalah studied over the inner surface of the cone with a geometry as belajar di atas permukaan batin kerucut dengan geometri sebagai defined with the sketch in Fig. ditetapkan dengan sketsa pada Gambar. 11. 11. In this figure, Dalam gambar ini, represents mewakili ring index corresponding for the -axis of the conical cup. indeks cincin sesuai untuk sumbu dari cangkir kerucut. This Ini has a maximum index of 10 corresponding to the different fiber memiliki indeks maksimum dari 10 yang sesuai dengan serat yang berbeda ring numbers in the prototype cup. cincin angka dalam cangkir prototipe. in Fig. pada Gambar. 11 represents 11 mewakili the source or detector indices, respectively, within a given sumber atau detektor indeks, masing-masing, dalam suatu fiber ring in the cup. cincin serat dalam cangkir. It corresponds to the horizontal axis with Ini sesuai dengan sumbu horizontal dengan an fiber number changing from 30 for the top ring to 21 for suatu jumlah serat berubah dari 30 untuk cincin atas 21 untuk Page 6 Halaman 6 1148 1148 IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS, VOL. IEEE JOURNAL OF DIPILIH Forum di QUANTUM ELECTRONICS, VOL. 5, NO. 5, NO. 4, JULY/AUGUST 1999 4, Juli / Agustus 1999

the bottom ring. cincin bagian bawah. For Fig. Untuk Gambar. 10, this number gives the detector 10, jumlah ini memberikan detektor number nomor for each ring number, . untuk setiap nomor cincin,. The intensity difference plots in Fig. Perbedaan intensitas plot pada Gambar. 10 are given on a 10 adalah diberikan pada logarithmic scale for the intensity. skala logaritmik untuk intensitas. These clearly show the Ini jelas menunjukkan shadow of the 10-mm diameter black bead as the dark area bayangan dari 10-mm diameter manik-manik hitam sebagai daerah gelap centered at about berpusat di sekitar (seventh ring from the bottom) (tujuh cincin dari bawah) and dan (15th detector fiber from the reference arrow). (Ke-15 detektor serat dari referensi panah). Such shadows also appear in the data from the patients, but Bayangan seperti itu juga muncul dalam data dari pasien, tetapi with a much lower resolution and with more noise due to dengan resolusi yang jauh lebih rendah dan dengan lebih kebisingan akibat tissue heterogeneity. heterogenitas jaringan. The area to the left of the shadow, with Area di sebelah kiri bayangan, dengan the measured high intensity difference, in Fig. yang diukur perbedaan intensitas tinggi, pada Gambar. 10 is one of 10 adalah salah satu dari the parasitic effects in our measurements coming from the efek parasit dalam pengukuran kami yang berasal dari time dependent drifts in the properties of the matching fluid waktu tergantung hanyut dalam sifat-sifat fluida yang cocok surrounding the phantom. seputar hantu. Although we try to subtract the Meskipun kami mencoba untuk mengurangi main contributions of this fluid by using the data of the kontribusi utama dari cairan ini dengan menggunakan data dari reference, the results are not perfect. referensi, hasilnya tidak sempurna. The time difference Perbedaan waktu between the real measurement and the reference measurement antara yang nyata referensi pengukuran dan pengukuran still results in imperfect cancellations of the effects of the masih menghasilkan pembatalan tidak sempurna efek average background medium, the matching fluid in this case. latar belakang rata-rata menengah, yang cocok cairan dalam kasus ini. The shadow of the bead discussed in these figures will be Bayangan manik-manik yang dibahas dalam angka-angka ini akan used in our discussions section to introduce a new concept for digunakan dalam bagian diskusi kita untuk memperkenalkan konsep baru untuk diffuse optical tomography based on the statistical properties baur tomografi optik berdasarkan statistik sifat of such transmission projections in our cup. transmisi seperti proyeksi dalam cangkir. The matching fluid discussed above is chosen according to Fluida yang cocok dibahas di atas dipilih sesuai actual measurements taken from volunteers. pengukuran aktual yang diambil dari sukarelawan. Its optical prop- Its optik prop

erties, such as the scattering and absorption coefficients, are erties, seperti penyebaran dan penyerapan koefisien, adalah chosen to match to the properties of the average breast tissue. dipilih untuk cocok dengan properti dari rata-rata jaringan payudara. This criteria is normally tested by plotting the attenuation Kriteria ini biasanya diuji dengan memplot pelemahan constant obtained from the patients themselves within the fluid. konstan diperoleh dari pasien itu sendiri dalam cairan. As described above, the attenuation constant is defined within Seperti dijelaskan di atas, pelemahan konstan didefinisikan dalam the diffusion approximation and found by fitting a straight line aproksimasi difusi dan ditemukan dengan memasang garis lurus to the measured data in a semilogarithmic plot. ke data diukur dalam sebuah plot semilogarithmic. This uses the Ini menggunakan expression, ekspresi (2) (2) where di mana is the injected laser intensity into the cup, adalah intensitas laser disuntikkan ke dalam cangkir, is the adalah attenuation coefficient, and pelemahan koefisien, dan is the distance from the source adalah jarak dari sumber fiber to the detector fiber. serat ke serat detektor. An example fit to the data taken Contoh sesuai dengan data yang diambil from one of the volunteers is shown in Fig. dari salah satu relawan ditunjukkan pada Gambar. 12. 12. This fit and Ini cocok dan other computations will be described in more detail in the next perhitungan yang lain akan dijelaskan secara lebih rinci dalam selanjutnya section when we discuss our approaches for the tomographic bagian ketika kita membahas pendekatan kami untuk tomografi image reconstruction. gambar rekonstruksi. Before we close this section, we would like to briefly Sebelum kita menutup bagian ini, kami ingin sebentar describe the effects of the noise in the measurements. menggambarkan efek dari kebisingan dalam pengukuran. This Ini will be helpful in introducing our topic on statistical nature akan sangat membantu dalam memperkenalkan topik kita di alam statistik of the tomography in the discussion section later. dari tomografi dalam diskusi di bagian lain. In its basic Pada dasarnya form, the noise effects the real signal from an inhomogeneity bentuk, efek suara sinyal nyata dari inhomogeneity of interest, at both high and low total intensity limits. bunga, di kedua tinggi dan rendah intensitas total batas. The Itu presence of an inhomogeneity can be measured by both keberadaan inhomogeneity dapat diukur dengan baik relative and absolute intensity changes it causes. relatif dan mutlak itu menyebabkan perubahan intensitas. In cases Dalam kasus where the quantity of interest is the absolute change due to the mana jumlah bunga adalah perubahan mutlak karena

inhomogeneity, one needs to measure at the shortest distances inhomogeneity, orang perlu untuk mengukur pada jarak terpendek to the source and the inhomogeneity itself. ke sumber dan inhomogeneity itu sendiri. This gives the Ini memberikan best sensitivity for detecting objects in this case. sensitivitas terbaik untuk mendeteksi bendabenda dalam kasus ini. However, Akan tetapi, one should not forget that the returning original source signal orang tidak boleh lupa bahwa sumber aslinya kembali sinyal levels from the shorter distances are also high. tingkat dari jarak pendek juga tinggi. At this high Pada tinggi intensity levels, the bit noise in our digitization circuitry limits tingkat intensitas, bit kebisingan di sirkuit digitalisasi kita batas the signal. sinyal. In cases where we measure the relative change due Dalam kasus-kasus di mana kita mengukur perubahan relatif karena Fig. Gambar. 12. 12. Attenuation constant fit to the transmitted intensity data taken from Pelemahan terus-menerus sesuai dengan intensitas yang ditransmisikan data yang diambil dari the breast of one of the volunteers at the laser wavelength of 870 nm. dada salah satu sukarelawan pada panjang gelombang laser 870 nm. The Itu fit indicates that the optical properties of the fluid surrounding the breast cocok menunjukkan bahwa sifat optik dari fluida yang mengelilingi payudara provides a good optical match. menyediakan optik yang baik cocok. to the inhomogeneity, we need to still stay at the shortest ke inhomogeneity, kita perlu untuk tetap tinggal di terpendek distances to the inhomogeneity but remain as far away from jarak ke inhomogeneity tetapi tetap sebagai jauh dari the source as possible. sumber mungkin. In this case, we measure low intensity Dalam kasus ini, kita mengukur intensitas rendah levels and the signal is limited by the statistical noise limit of tingkat dan sinyal dibatasi oleh batas kebisingan statistik our detectors. detektor kita. Therefore, the optimization for the detection of Oleh karena itu, pengoptimalan untuk mendeteksi an inhomogeneity will actually take place in the measurement sebuah inhomogeneity akan benar-benar terjadi pada pengukuran region between these two limiting cases. wilayah antara kedua membatasi kasus. Most tomography Kebanyakan tomography methods which have been tried up to now, seem to ignore metode yang telah mencoba sampai sekarang, tampaknya mengabaikan this region. daerah ini. This data region has special emphasis within the Data ini wilayah mempunyai penekanan khusus dalam statistical tomography method discussed later in the section statistik metode tomografi dibahas kemudian dalam bagian on ongoing research. pada penelitian berkelanjutan. V. T V. T OMOGRAPHY OMOGRAPHY To be able to probe an optically diffuse medium, the Untuk dapat menyelidiki menyebar secara optikal media, yang breast in our case, the measurements of the transmitted output payudara dalam kasus kami, dengan pengukuran output yang ditransmisikan

intensity are made at a specific set of detector positions intensitas yang dibuat pada set tertentu detektor posisi following the scattering of light injected from another set of mengikuti penyebaran cahaya disuntikkan dari satu set source positions posisi sumber . . This tomographic measurement geometry Pengukuran tomografi ini geometri is shown schematically in Fig. diperlihatkan secara skematik pada Gambar. 13. 13. In order to be able to Dalam rangka untuk bisa obtain a 3-D image showing the variation of tissue properties memperoleh gambar 3-D menunjukkan variasi jaringan properti inside the breast, a reconstruction algorithm is required to deal di dalam dada, sebuah algoritma rekonstruksi diperlukan untuk menangani with the very high turbidity of the breast tissue. dengan kekeruhan sangat tinggi dari jaringan payudara. However, Akan tetapi, with the 65 000 data points from the source and detectors in dengan data 65 000 poin dari sumber dan detektor di our experimental system, and large number of corresponding sistem eksperimental kami, dan jumlah besar sesuai voxels in the image, the problem is not very trivial for voxels dalam gambar, masalahnya tidak terlalu sepele untuk real-time clinical applications. real-time aplikasi klinis. We have to actually devise Kita harus benar-benar merancang relatively simple tomographic methods to remain practical in metode tomografi relatif sederhana untuk tetap praktis dalam our computations. perhitungan kami. In our work, as described below, we have Dalam pekerjaan kami, seperti yang dijelaskan di bawah ini, kami telah tried several such methods for reconstructing tomographic mencoba beberapa metode untuk merekonstruksi seperti tomografi images. gambar. These methods are all based on the model where the Metode ini semua didasarkan pada model di mana tissue is represented simply by an isotropic diffuse medium. jaringan hanya diwakili oleh baur isotropik medium. Therefore, before we describe the details of the tomography Oleh karena itu, sebelum kami menjelaskan rincian tomography methods employed in this study, we first outline the basics of metode yang digunakan dalam studi ini, pertama-tama kita garis besar dasar-dasar the diffuse medium model used in this study. menengah yang tersebar model yang digunakan dalam studi ini. Page 7 Halaman 7 COLAK et al. : CLINICAL OPTICAL TOMOGRAPHY AND NIR SPECTROSCOPY FOR BREAST CANCER DETECTION COLAK et al.: KLINIS OPTIK spektroskopi NIR tomography DAN UNTUK KANKER PAYUDARA DETECTION 1149 1149 Fig. Gambar. 13. 13. The geometry defining the light projections used for the tomoMendefinisikan geometri proyeksi cahaya yang digunakan untuk tomo graphic image reconstructions. gambar grafik rekonstruksi. A diffuse medium can be characterized by a pair of parame- Sebuah media baur dapat dicirikan oleh sepasang parameter -

ters, called the scattering and absorption coefficients, Ters, yang disebut koefisien hamburan dan penyerapan, and , dan, respectively, already discussed in the previous section. masing-masing, sudah dibahas pada bagian sebelumnya. Using Menggunakan this simple model in the diffusion equation in homogeneous model sederhana ini dalam persamaan difusi homogen medium, we find that the output intensity, in phot/(s-cm menengah, kita menemukan bahwa intensitas output, dalam PHOT / (s-cm is adalah given by [35] diberikan oleh [35] (3) (3) where di mana is the distance from the source location, adalah jarak dari lokasi sumber, is the adalah source term, in phot/s units, injecting photons into the medium, istilah sumber, di PHOT / s unit, menyuntikkan foton ke dalam medium, is the photon diffusion coefficient (in adalah koefisien difusi foton (dalam cm) and cm) dan is the attenuation constant. adalah pelemahan konstan. is a adalah dimensionless constant dependent on the collection geometry, konstan berdimensi koleksi tergantung pada geometri, where we assumed that we have a certain collection area at the di mana kita beranggapan bahwa kita memiliki koleksi tertentu daerah di output fiber, ignoring any corrections due to the detector solid keluaran serat, mengabaikan semua koreksi karena detektor padat angle. sudut. Since we obtain our images with respect to a reference, Karena kita memperoleh gambaran kita terhadap referensi, this assumption is not expected to introduce large errors. asumsi ini tidak diharapkan untuk memperkenalkan kesalahan besar. Approaches of this sort has been found to describe the Pendekatan semacam ini telah ditemukan untuk menggambarkan distribution of photons in highly scattering media, with a few distribusi sangat hamburan foton dalam media, dengan beberapa heterogeneities, rather well [36][39]. heterogeneities, cukup baik [36] - [39]. However, it should be Namun, itu harus noted that its application to problems with real biological tissue mencatat bahwa penerapannya masalah dengan jaringan biologis nyata is still to be proven. masih harus dibuktikan. If one desires to have a solution to the Jika salah satu keinginan untuk memiliki solusi untuk diffusion equation for general object shapes and strengths there persamaan difusi untuk objek umum bentuk dan kekuatan di sana are also rigorous analytical and numerical techniques. juga ketat teknik analitis dan numerik. This Ini is not needed for our present study. tidak diperlukan untuk studi kita sekarang. It only complicates the Hanya merumitkan computations unnecessarily. perhitungan yang tidak perlu. The output intensity equation discussed above, does not Persamaan intensitas output yang dibahas di atas, tidak

provide a direct assignment of the value of the transmitted memberikan penugasan langsung dari nilai yang ditransmisikan intensity back to the object's real space in the medium. intensitas kembali ke objek ruang nyata dalam medium. For that Untuk we study the photon path distributions which are given by the kita mempelajari jalur distribusi foton yang diberikan oleh response of the system to a point perturbation in the medium. respon dari sistem ke sebuah titik kekacauan dalam medium. To be able to find the functional form of this distribution, Untuk dapat menemukan bentuk fungsional distribusi ini, we consider a single source-detector pair and assume that we kami mempertimbangkan sumber-detektor tunggal pasangan dan menganggap bahwa kita have an absorbing point object at a position memiliki titik menyerap objek pada posisi within the dalam scattering medium. media penyebaran. The total photon density at a position Foton total densitas pada posisi elsewhere in the medium changes due to the presence of this di tempat lain dalam perubahan media karena keberadaan point perturbation by a banana-like function [38], [39]. titik Usikan oleh seperti pisang-fungsi [38], [39]. The Itu simplified form for this perturbation function bentuk yang disederhanakan untuk fungsi Usikan for an untuk absorbing point is shown in Fig. titik menyerap ditunjukkan pada Gambar. 14 with a surface plot. 14 dengan plot permukaan. Fig. Gambar. 14 14 is only an example given for source and detector positions hanyalah sebuah contoh yang diberikan untuk posisi sumber dan detektor at di and dan where the parameters mana parameter mm and mm /mm are used. / mm digunakan. Furthermore, this Lebih jauh lagi, ini plot represents the perturbation function only in the plot mewakili fungsi Usikan hanya dalam Fig. Gambar. 14. 14. Perturbation function Gangguan fungsi P (r; r1) P (r; r1) defining the region of highest sen- mendefinisikan wilayah tertinggi sen sitivity to a point object between the source and the detector. sitivity ke objek titik antara sumber dan detektor. The parameters Parameter to obtain this example are discussed in the text. untuk memperoleh contoh ini dibahas dalam teks. plane, and the actual 3-D shape of this function pesawat, dan 3-D sebenarnya bentuk fungsi ini can dapat be obtained by rotating the shape around the dapat diperoleh dengan memutar bentuk di axis. sumbu. Further Lebih jauh discussion on this function can be found in [35]. pembahasan mengenai fungsi ini dapat ditemukan di [35]. The meaning of the perturbation function Arti dari gangguan fungsi discussed dibahas

above can be explained as follows. di atas dapat dijelaskan sebagai berikut. If in a diffuse optical Apabila dalam suatu baur optik tomography experiment, an intensity (or photon density) mea- tomography percobaan, intensitas (atau kerapatan foton) mea surement differs from an expected value, then the cause of this surement berbeda dari nilai yang diharapkan, maka penyebab ini difference can be assigned to any point in the object space Perbedaan tersebut dapat ditetapkan untuk setiap titik dalam ruang obyek according to the strength of the perturbation function. sesuai dengan kekuatan fungsi gangguan. In fact, Bahkan, the strength of the perturbation causing the observed difference kekuatan Usikan menyebabkan perbedaan yang diamati is inversely proportional to the value of berbanding terbalik dengan nilai . . Needless to Perlu say, in a highly heterogeneous medium, such regions can have mengatakan, dalam media yang sangat heterogen, daerah tersebut dapat memiliki complicated shapes. rumit bentuk. Nevertheless, for a medium consisting of Namun demikian, untuk media yang terdiri dari weak inhomogeneities, this perturbation function introduces inhomogeneities lemah, fungsi Usikan ini memperkenalkan the notion of the highest probability light paths in such a pengertian tentang jalan cahaya probabilitas tertinggi sedemikian diffuse medium. baur media. As we will discuss below, this notion can Seperti yang akan kita bahas di bawah ini, pengertian ini dapat be utilized to obtain a practical algorithm for our image dimanfaatkan untuk mendapatkan algoritma praktis untuk foto kami reconstruction problem. masalah rekonstruksi. It is clear that the resolution of imaging in diffusive media Jelas bahwa resolusi dari pencitraan di media difusif depends on the width of these banana shaped perturbation tergantung pada lebar pisang ini berbentuk Usikan regions, regardless of how distorted they may be. daerah, terlepas dari bagaimana terdistorsi mereka mungkin. As implied Seperti yang tersirat in this discussion, the projections of the objects embedded dalam diskusi ini, proyeksi dari benda tertanam in diffusive media will be blurred. dalam difusif media akan menjadi buram. Comparing the simplified Membandingkan disederhanakan form for the perturbation function, with the straight line for formulir untuk fungsi Usikan, dengan garis lurus untuk the X-Ray projections, we see that in optical tomography, X-Ray proyeksi, kita melihat bahwa dalam tomografi optik, what we effectively get is that, the line integral for the XRay absorption is replaced by the volume integral for the diffuse optical attenuation. This volume is actually defined within the volume of the banana of the perturbation function. Within this assumption of the banana shape path, we find that the full width at half maximum broadening for a point object is approximately sekitar . . If the distance between the source and detector is taken to be 10 cm, then an attenuation

constant of /m yields a broadening of 3.6 cm, and dan /m reduces this width to 3.1 cm. Choosing a Memilih wavelength such that is further increased would enhance the resolution, but this will also require an even larger dynamical range for the detector in our system. Page 8 Halaman 8 1150 1150 IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS, VOL. 5, NO. 5, NO. 4, JULY/AUGUST 1999 After defining these light paths in the diffuse medium, we now have to make a decision on the quantity to be plotted in the images. gambar. There are many possible quantities which could be used as the imaged quantity in optical tomography in diffuse media. These possibilities are: the attenuation coefficient, absorption/scattering coefficients, diffusion coefficient, the perturbation parameters, the differences of such parameters at two wavelengths, their time dependencies/constants etc. In our work we choose the attenuation coefficient to be the menjadi preferred quantity to represent our images in. This quantity can be easily computed by using different source detector distances as done in the previous section. Furthermore, since we have a set of reference measurements available, we can also obtain differences in the attenuation coefficients by comparing the real measurements to this reference set. This is also advantageous for noise considerations in the fan beam geometry, because of the high intensity contrast coming from the large variation in the source and detector distances. In summary, due to these arguments, we choose to present the results of our measurements in terms of the attenuation coefficient koefisien in units of m . For images we use the itu difference between the attenuation coefficient of the tissue dari jaringan and dan of the homogeneous reference medium. As emphasized at the beginning of this section, in order to deal with 65 000 data points and a large number of voxels in practical manner, we first devised a simple backprojection method based on the X-Ray tomography principles [40], [41]. The main difference in this approach as compared to the conventional X-Ray tomography is that we replace the projection lines with the banana perturbation paths described above. In Di this paper, we only give a brief description of this method because the details were presented earlier [35]. Basically, in

this approach, we first obtain an average attenuation constant from the measurements in order to be able to define a banana width. lebar. This width is then used to spread the effects of a perturbation, given in terms of the difference in the attenuation coefficient, back to the image space. This procedure is repeated Prosedur ini diulang for all source detector positions. Since in our geometry the filtering by the filter [40] is not straightforward, we ignore it. mengabaikannya. Actually, the broadening due to this effect is Efek ignorable as compared to the blurring due to optical diffusion effects. efek. It should be noted that, within this simple approach, we also ignored all the refraction effects present in optical projections. proyeksi. This would be important if we were dealing with much stronger inhomogeneities in the scattering medium as compared to the tenuous biological tissue. The application of the simple tomography method described above to our experiments is demonstrated in Fig. 15. 15. The Itu multiplanar optical tomography pictures shown in this figure are obtained from a phantom prepared by placing a 10-mm diameter sapphire bead in a tissue-like scattering fluid. This Ini fluid was composed of a 1% intralipid solution in water. The Itu sapphire bead was painted black on its surface and the test was done by using a 780-nm laser. The definition of the Definisi planar images are shown in Fig. 16, where different axis give the normal directions to each planar image. Specifically, the Khusus, circular cross sectional image, in Fig. 15, is at a horizontal plane normal to the axis of the cup. The conical cross Fig. Gambar. 15. 15. The multiplanar tomography images, at 780 nm, of a 10-mm diameter black bead in a tissue-like scattering fluid of 1% intralipid solution in water. dalam air. Red regions indicate high attenuation, and point to the location of the bead placed in the intralipid correctly. Fig. Gambar. 16. 16. The definition of the planes used in images shown in Fig. 15. 15. Different axes shown here define the normal directions to each planar image in Fig. pada Gambar. 15 as described in the text. section images on the right side and below this circular image are the vertical planes normal to the and axes, respectively. masing-masing. The right side of this circular cross sectional image corresponds to the reference point in our prototype cup as indicated in Fig. 16 with a thick horizontal arrow at the rim of the cup. The red areas in these images are the areas of highest attenuation within the cup. These areas point to the known location of the black bead placed in the intralipid correctly. benar. As discussed before, these optical tomographic images in Fig. 15 show the degree of optical blurring clearly. Some of our present efforts are directed toward adapting our algorithms to apply Fourier deconvolution methods to sharpen these images as was described for simpler geometries before [35]. [35]. Some of our preliminary results in this direction will be discussed later in this paper. dibahas kemudian dalam makalah ini.

Page 9 Halaman 9 COLAK et al. : CLINICAL OPTICAL TOMOGRAPHY AND NIR SPECTROSCOPY FOR BREAST CANCER DETECTION 1151 TABLE I TABEL I RR ESULTS FROM CC LINICAL LINICAL TT RIALS Real The simple backprojection method described above is successful in obtaining images of acceptable resolution up to a limited degree. In some instances, the inhomogeneities can be missed with this method. In order to improve the quality of the resultant images, we have developed a tomography algorithm based on the algebraic reconstruction technique (ART), capable of generating quantitative reconstructions from the data relative to the homogeneous reference measurements describe above. This approach is based on a perturbative approach [42], and a brief description was presented earlier [19]. [19]. In this technique, the perturbation is spread back to the image space in a similar fashion as described in the banana method described above. metode yang dijelaskan di atas. Except that, in ART, the image is updated, or corrected, after each iteration. The corrections at each step are determined by the difference of the measured data from a set of computed data found from the image reconstructed in the previous iteration. These iterations are repeated till an error measure is minimized as common to other ART-based approaches [43]. VI. VI. C C LINICAL LINICAL RR ESULTS ESULTS A summary of the results from our clinical trials is presented in Table I. During this first trial phase we have tested 14 patients with the detectability of the inhomogeneities as our main focus. In this procedure, the information from X-Ray and ultrasound images were available to us prior to our optical measurements. pengukuran. Our goal was to check if the inhomogeneities diagnosed by standard clinical methods could also be detected in our optical images. As Table I shows, our detection rate of the inhomogeneities is about 90%. The measurements done on patients which are not reported in the table failed due to experimental malfunction before imaging phase could be reached. tercapai. In the following paragraphs in this section, we will focus on a few of the cases from Table I and describe what we mean by the phrase visible in the table. azm01: Medullar Carcinoma

The carcinoma of this patient was in the inner side of her right breast. The most straightforward result from this patient is the raw optical transmission image corresponding to the geometry described in Figs. 10 and 11. 10 dan 11. This result is shown in Fig. Gambar. 17 as a color coded projection image on the cone surface. The cancerous area, as determined from the X-ray images from the patient, appears as a red, high attenuation, area in the top center of the optical image. This red part has a quantitative value of 0.15/mm for the attenuation constant, and some of the deeper blue parts corresponds to 0.09/mm attenuation. This Ini projection image was taken by a 780-nm laser light. The two X-Ray mammography pictures shown in Fig. 18 18 are taken from the right (R) breast of the same patient (azm01) with a breast cancer. In both the CC (top to down) and the MLO (right to left) views, a large dense mass in the order of 12 cm is clearly visible. The images are flipped around in order to make it easier to compare with the corresponding optical images discussed below. The tomographic multiplanar images in Fig. 19 show how this tumor appears in the optical mammograms obtained by our optical mammography prototype system from the right breast of the patient azm01. The reconstruction was done by the simple backprojection method based on the banana perturbation function described in the previous section. These images use the color coding normalized between 0 (blue) and 1 (red), corresponding to the lowest and highest absorptive perturbations in the transmitted intensity through the breast. payudara. This is shown as the local difference between the attenuation coefficient of the tissue and the homogeneous reference medium obtained both at a wavelength of 786 nm. nm. As in the previous image, the red region indicates the strongest parts of the inhomogeneities. Clearly visible is the absorbing structure in the breast. Histological examination Pemeriksaan histologis determined this to be a medullar carcinoma, with a size of about two centimeters. Its location agrees reasonably well with the location of the cancerous lesion observed in the X-ray mammograms. As mentioned before, the optical tomographic images show a large degree of optical blurring. At the present Saat ini time, we are adapting our algorithms and using other new methods to reduce the effects of this blurring. The image in Fig. Gambar pada Gambar. 20 shows the 3-D view of the reconstructed image of the cancer in the same right breast. This Ini image is also obtained at a laser wavelength of 780 nm. The isocontour of the inhomogeneity on the left is obtained at normalized 0.9 value and, as indicated above, its location agrees well with the location which can be deduced from the X-ray mammo pictures given above. The cone like surface is Page 10 Halaman 10 1152 1152

IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS, VOL. 5, NO. 5, NO. 4, JULY/AUGUST 1999 Fig. Gambar. 17. 17. The transmitted light through the right breast of the patient azm01 when illuminated from a source fiber from the reference direction at 780 nm. nm. This is a raw projection indicating the attenuation coefficient through the breast toward the detectors. The cancerous area, appears as a red, high attenuation, area in the top center of the image. Fig. Gambar. 18. 18. X-Ray mammogram images from the right breast of patient azm01. shown only to indicate the boundaries of the cup. Right side of this cup corresponds to the position of the right arm of the patient as the data was being taken. This is the side labeled as the reference point in the photo of our prototype system in Fig. pada Gambar. 3. 3. azm05: Cyst This patient was suspected of having a large cyst on the outer part of her left breast. It is worthwhile to emphasize that, in most cases involving a cyst, the X-ray mammograms do not give clear evidence on the presence of such inhomogeneities in the breast. In such cases, ultrasound images are obtained. Such an image corresponding to the left breast of this patient is shown in Fig. ditunjukkan pada Gambar. 21. 21. This ultrasound image clearly shows a large region with no sound reflections. Having a postfocusing effect below this region indicates that the inhomogeneity is a cyst rather than a tumor. Multiplanar cross section optical tomography images of the left breast of this patient is given in Fig. 22. 22. The reconstruction was done by the iterative ART method described in the previous section. bagian sebelumnya. This figure shows the local difference in attenuation constant between the attenuation coefficient of the tissue and the homogeneous reference medium, both obtained at a wavelength of 658 nm. Clearly visible is a less absorbing structure (dark blue area) in the breast. As Sebagai mentioned above, the histological examination determined this Fig. Gambar. 19. 19. Multiplanar cross section optical tomography images of the right breast of patient azm01. The sketch on the right indicate the location of the cancerous lesion which corresponds to the location of the high attenuation, red, are in the images. Fig. Gambar. 20. 20. The 3-D isocontour view of the reconstructed image of the cancer in the right breast of azm01. The isocontour of the inhomogeneity on the left is obtained at normalized 0.9 value. to be a cyst, with a size of about 3 cm. The location of this dark blue area in these images correlates well with the known position of the cyst in patient's left breast. The low attenuation blue regions correspond to an attenuation constant of about , while the surrounding red areas represent an attenuation constant around 125 m . These red areas in these images are believed to correspond to high density areas of the patients breast. It should be noted that in the absence of prior information about the patient, such distinctions from cancerous areas, could not be made unambiguously.

azm06: Adenocarcinoma This patient had a tumor on the top outer side of her left breast. Subsequent diagnosis identified this as an adenocarcinoma of about 1 cm size. Multiplanar cross-sectional optical tomography images of the left breast of this patient is given in Figs. pada Gambar. 23 and 24. The images in Fig. 23 were obtained Page 11 Page 11 COLAK et al. : CLINICAL OPTICAL TOMOGRAPHY AND NIR SPECTROSCOPY FOR BREAST CANCER DETECTION 1153 1153 Fig. Gambar. 21. 21. Ultrasound reflection image from the left breast of patient azm05. The large black area, toward the top indicate the cyst region. Fig. Gambar. 22. 22. Multiplanar cross-sectional optical tomography images of the left breast of the patient azm05 with a cyst. The dark blue area correlates well with the known position of the cyst. The image was taken at 658 nm. by the backprojection method, and the ones in Fig. 24 was obtained the iterative ART method, both described in the previous section. bagian sebelumnya. Both approaches identify the approximate location of the adenocarcinoma correctly. Except that, due to the instabilities involved in the iteration cycles of the ART method, there are additional contrast features in the images which introduces ambiguity. VII. VII. S S PECTROSCOPY For optical transillumination to be successful in being sensitive and specific for breast cancer detection, we need to be able to distinguish different tissue characteristics from such optical measurements. It is therefore of critical importance to know the variation in the attenuation constants of dari both the normal and the diseased tissue. Unfortunately, the Sayangnya, results related to the spectroscopy in our clinical studies were Fig. Gambar. 23. 23. Multiplanar cross-sectional optical tomography images of the left breast of the patient azm06 with an adenocarcinoma. The red area toward the left in the circular horizontal cross section correlates well with the known position of the adenocarcinoma close to the left arm. The image was obtained by our simple backprojection method described in the previous section. Fig. Gambar. 24. 24. Multiplanar cross-sectional optical tomography images of the left breast of the patient azm06 with a adenocarcinoma. This set of images was obtained by our ART technique. As indicated for the previous figure, the red area toward the left in the circular horizontal cross section correlates well with the known position of the adenocarcinoma close to the left arm. Other Lain inhomogeneities appearing blue for low attenuation areas are probably related to the iteration instabilities involved in this reconstruction technique. probably the most dissapointing aspects of our work. Although Meskipun we will try to summarize our results here briefly, overall, we must say that there were not sufficiently distinct features

Page 12 Page 12 1154 1154 IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS, VOL. 5, NO. 5, NO. 4, JULY/AUGUST 1999 Fig. Gambar. 25. 25. Comparison at two (pairs) wavelengths of the mean attenuation coefficient, K; K; for several volunteers. Correlation seems to be strong, indicating that the heterogeneity of the tissue overshadows any effects specific to inhomogeneities. which we were able to find in our imaging efforts. This Ini result is probably related to the arguments we raised on the heterogeneity of the tissue in our tissue optics section. Prior to our clinical trial phase, we have measured the average attenuation coefficient of the uncompressed breasts of 17 volunteers, aged between 28 and 58 at wavelengths of 660, 780, and 920 nm. The results were fit to the output intensity expression, described earlier, in order to obtain an average attenuation constant at different wavelengths for different volunteers. sukarelawan. We found that for 920 nm, probing CH bonds (fat), the attenuation constant, is approximately 150 m for most volunteers. We have also found values ranging in between (80160) m for 660 nm, and (70140) m for untuk 780 nm. For some volunteers, the breasts were too opaque (greater than 160 m at the third laser wavelength, 920 nm. nm. This is probably due to the added effects of the nearby water absorption band at around 980 nm as discussed in the section on tissue optics. Despite the high dynamic range of our detectors, we were not able to obtain images with sufficiently small noise content even at laser powers of 50 mW at this wavelength. panjang gelombang. This is the reason why most of our measurements for the clinical trials were done by replacing this laser by another one operating at 870 nm. Although the measured values for these volunteers showed a large scatter, we have found that the correlation between different sets of wavelengths is very strong. For example, the Sebagai contoh, attenuation coefficient for different volunteers at 780 nm is closely related to the ones at 660 nm. Specifically, we found that the attenuation constants at 786 nm, is related to those at 658 nm, simply by As both Ketika kedua of these wavelengths are located on the falling edge of the Hb absorption peak, this correlation should not come as a surprise. The results of this study showing the correlation of the average attenuation constants at two different pairs of

Fig. Gambar. 26. 26. Comparison at two (pairs) wavelengths of the local attenuation coefficient koefisien KK for a given breast of the patient azm06. From this and also from other measurements made on other patients, we conclude that these types of plots also shows a high degree of correlation between different pairs of wavelengths. dari panjang gelombang. The gray scale indicates a range of 0500 counts from lightest to the darkest gray. laser wavelengths for different volunteers are summarized in Fig. Gambar. 25. 25. We have repeated the types of study described above for each individual patient but by focusing on finding any spectral distinctions at different locations within that breast. As the Sebagai reconstruction algorithm for one of our methods, ART, is rather quantitative with sharper features, we attempted to make a histogram of the assigned values, at every individual position in a given breast, to compare the behavior at two different wavelengths. panjang gelombang yang berbeda. After this procedure, we usually found a spread of about 40 m within each breast image. This Ini variation is less than the variation between different volunteers, as discussed above. Nevertheless, given the correlation between the measurements for the average and dan , we Kami have also investigated the correlation between them within a breast. The results are quite noisy and not easily conclusive. However, we found that most reconstructed values follow the itu dependence described above for the behavior describing different patients. Fig. Gambar. 26 shows a typical correlation plot for patient azm06 as an example. VIII. VIII. O O NGOING RR ESEARCH ESEARCH From the two previous sections, it is clear that our clinical trials give sufficient hope for the detection of inhomogeneities in female breast by optical tomography. However, for correct diagnosis, one has to also identify the nature of an inhomogeneity. geneity. That is, one should be able to tell if a high attenuation area is from a cancerous lesion or from the natural variations in the density of the breast tissue. Considering the differences in the properties of breast tissue in different individuals, some sort of optical signature for cancer is highly desirable. In Di order to improve our optical method toward this direction, our present emphasis focuses on improving our reconstruction

techniques for better resolution and also disentangling the scattering and absorption coefficients of the tissue from each other. lain. As described earlier, the diffuse broadening on the size of an object, placed near the middle of the cup, is in the order of a centimeter. Although we do not expect to compete with the submillimeter resolution of X-ray imaging, it is still highly desirable to sharpen our optical images, to facilitate the extraction of spectroscopic information. As discussed in Sebagaimana dibahas dalam the previous section, the extraction of reliable spectroscopic Page 13 Halaman 13 COLAK et al. : CLINICAL OPTICAL TOMOGRAPHY AND NIR SPECTROSCOPY FOR BREAST CANCER DETECTION 1155 1155 Fig. Gambar. 27. 27. The breast phantom constructed from delrin. The blackened part on the small cylinder, appearing outside, represents a high-attenuation section to mimic a cancerous lesion to be imaged. information is quite difficult with the added diffuse blurring in the image features. In this section, we will describe our ongoing studies aimed toward improvements in these areas briefly. sebentar. Deblurring: In a previous paper [35], we have described a deconvolution technique to sharpen images of objects embedded in diffuse media. Since the diffusion creates a spatially dependent point spread function, this method works only in conjunction with spatially dependent deconvolution techniques. niques. As we had described earlier [35], such approaches have already been applied in image restoration, including medical images taken by computed tomography [44] and electrical impedance tomography [45]. Without going into detail, we would like to present a resulting image from our studies done by using a phantom in our prototype. The Itu phantom and the images before and after deblurring are shown in Figs. pada Gambar. 27 and 28. The deblurring for this case has been done only for a single circular ring. The phantom, shown in Fig. pada Gambar. 27, represents the model of the female breast formed in delrin material containing a single inhomogeneity. The Itu inhomogeneity itself is also delrin, except that it is blackened by paint to have a higher attenuation constant in order to represent a cancerous lesion. As seen from the tomographic images given in Fig. 28, this small inhomogeneity is not observable prior to the deconvolution of the image. The details of the deblurring technique is described in sufficient detail in our previous report [35] and will not be repeated here. We Kami have tried to extend this approach to the full volume of the cup geometry in our mammography prototype system. However, Akan tetapi, due to sharp cut off of the data at the rim of the cup, we did not have success with real experimental data. At the present Saat ini time, we are investigating the utilization of wavelet expansion methods on our data to go around the difficulty due to the

discontinuity at the rim of the cup described above. Scattering Versus Absorption: One of the difficulties in the tomographic methods we have employed in the present work is the treatment of the data coming from scattering and absorbing Fig. Gambar. 28. 28. The tomogaphic image of the blackened inhomogeneity shown in the previous figure. These results are presented only for a single cylindrical ring. cincin. The image on the right corresponds to the deblurred version of the original one on the left. Deblurring was achieved by a spatially varying deconvolution method described in an earlier paper [35]. Experimental data Data percobaan could not be deconvolved for the full cup volume due to difficulties associated with the discountinuities in data at the rim of the cup. objects in the same fashion. That is, for a given projection, we have made no effort to distinguish the direction dependent components coming from scattering objects and/or interfaces. Such components differ from those representing the isotropic contributions of the purely absorbing objects. This approach Pendekatan provided us with a simpler tomographic method to deal with, but at the expense of losing some information and perhaps some resolution. We describe this in more detail with the following discussion and propose a method which should in principle be applicable in practical situations with a little extra effort. upaya. In our previous paper on diffuse optical tomography [35], we have discussed the isotropic and dipole like scattering patterns of the absorbing and scattering objects. In order Agar to test these experimentally, we have placed two kinds of sapphire beads into the cup of our prototype system. As Sebagai usual these beads were embedded in a scattering intralipid solution representing tissue. In one experiment the saphire bead was coated black, representing an absorber, and in the other it was not coated, to represent a scattering perturbation. The shadows, or the scattering patterns of these beads in the two experiments are shown in Fig. 29 in the same geometry described in Fig. 11. 11. The two pair images (top and bottom) in each set correspond to different source positions. The top Atas image was obtained if the source was chosen in the top ring, and the bottom image was obtained if the source was chosen in the bottom ring. It is obvious from these sets that the dip for the scattering pattern of the absorbing bead remains at about the same location proving that it is indeed an isotropic scattering pattern. Meanwhile, the dip for the scattering pattern of the scatterer bead is moving from the bottom of the cup to the top on the opposite side of the cup. This, in its simplest form of conclusion, says that if one chooses to emphasize absorbing objects in the tomographic images, then only the autocorrelated parts of different projection images need to be taken into account. Starting from this assumption, we have developed a new tomographic method focusing on the statistical properties of projections, which is described next. Note that the difficulties of the tomographic methods due to the

common contribution of scatterers and absorbers were already mentioned in our previous report [35] in association with a set Page 14 Page 14 1156 1156 IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS, VOL. 5, NO. 5, NO. 4, JULY/AUGUST 1999 Fig. Gambar. 29. 29. The shadows of the two different beads corresponding to an absorbing (left) and a scattering (right) object embedded in intralipid solution. The two images in each set correspond to the cases where the source was chosen in the top ring (top) and the bottom ring (bottom). This source angle was chosen nearly opposite to the angular position of the beads in each case. It is obvious from these sets that the position of the dip of the absorbing bead remains at the same location as the source is shifted from top to bottom. Meanwhile the dip for the scatterer moves from the bottom of the cup to the top following the source motion in an out of phase fashion. The axes labels here are the same as in Fig. 10. 10. Fig. Gambar. 30. 30. The histogram obtained by counting the number of source-detector pairs which allow their perturbation to be assigned to a chosen point in the image space. of inconsistent images obtained from a phantom of chicken tissue at different wavelengths and matching liquid. Histogram Tomography: The basic approach of this method in forming tomographic images is to make sure that, at least a set of several source detector measurements are in consistent agreement in assigning an inhomogeneity in a given point in space. This technique has been tried by us on only a simple group of objects yet. The practical application of this method in the formation of an image is as follows. First, as described above, in order to decrease the effects of the scatterer contribution and also to decrease the noise, we only take the Fig. Gambar. 31. 31. This is the resulting tomographic image of the absorbing bead using the histogram approach described in the two previous figures. In practical Dalam praktis words, the surface plot represents the peak value of the sharp feature in the previous figure normalized to its width. This is a measure of consistency of many data points agreeing on the existence of an object in that location. accumulated portion of the projections. For the time being, this process is done simply by throwing away those components of data which are not repetitive in different projections. This Ini is the simplest way we can emphasize the autocorrelated portions of the projections. The results for the single bead example, discussed in Fig. 10, is taken as an example. Next, Berikutnya, for a given set of measurements we crudely count the number of source-detector pairs which allow their perturbation to be assigned to a chosen point in the image space. The Itu results of such a counting, or the resultant histogram, is plotted in Fig. diplot pada Gambar. 30 for this simple example. The sharp peaked feature indicates the measure of relative probability that the given set of data points would assign the existence of an inhomogeneity to the chosen location corresponding to this

whole plot. Furthermore, the strength of the object is given by the value on the axis, negative or absorbing in this case. kasus. The broader feature at the center shows the contributions from any other inhomogeneities including the effects of the boundaries. batas. By plotting the peak value of the sharp feature normalized to its width, as shown in Fig. 31, we obtain a corresponding tomographic image for the bead. As can be Seperti dapat seen, this method provides a better resolution and has the feature that it can emphasize either a purely absorbing or a scattering contributions from inhomogeneities. Although this Meskipun ini approach shows promise in obtaining improved resolution in diffuse optical tomography problems, its practicality for in vivo breast imaging has not been studied yet. IX. IX. C C ONCLUSION ONCLUSION In this paper, we have summarized the results from the first phase of clinical trials with the Philips optical mammography prototype system. This optical mammo prototype is used to image the interior of the female breast with the help of near-infrared (NIR) laser light transmission measurements. The main component of this system is a cup region, with 255 detector and 255 source fiber tips, where the full set of optical projections through the breast can be obtained within Page 15 Halaman 15 COLAK et al. : CLINICAL OPTICAL TOMOGRAPHY AND NIR SPECTROSCOPY FOR BREAST CANCER DETECTION 1157 1157 minutes in a clinical setting. In this study, we have also given descriptions and results of tomographic image reconstruction algorithms based on a modified version of the X-ray back projection method. The imaging results in the clinical environment with ten patients resulted in a 90% rate of detectability for a variety of inhomogeneities in patients' breasts, with prior knowledge from X-ray and ultrasound diagnosis. The Itu specificity of our results are, however, not acceptable yet, due to the difficulties in obtaining spectroscopic signatures of cancerous lesions in the high heterogeneity of the breast tissue. We believe that, in order to improve this aspect and achieve high specificity with optical methods, we have to pay more attention to the biomedical basics of the optical characteristics of tissue. To improve this aspect in our studies, we have proposed new avenues for disentangling tissue parameters and achieving better resolution in image reconstruction. We expect Kami mengharapkan that, with such improvements, and with the accumulation of clinical experience on tissue spectroscopy, the optical diagnosis/imaging methods can provide the basis for a versatile and safe mammography system. RR

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ages, in Electrical Impedance TomographyApplied Potential Tomography , special issue of Clinical Physics and Physiological Measurement , vol. vol. 8, supp. A, 1987, pp. 4754. 47-54. SB Colak received the Ph.D. degree in quantum electronics from the University of California at Los Angeles, in 1978. Since his graduation, he has been with Philips Research as Senior Scientist and/or Project Leader, first at Briarcliff Manor, NY, and then in Eindhoven, The Netherlands. Belanda. His work has been primarily on computational and theoretical modeling of various devices and physical phenomena. This includes topics such as laser light scattering, semiconductor electronic FET devices in Si and SiGe, rare-earth and transition-metal ion spectroscopy and lasers, band-offsets and electronic states in GaAs quantum-well structures, GaAs and ZnSe semiconductor injection lasers and electron beam pumped lasers, photoluminescence and electronic transport in IIVI semiconductors, second harmonic generation from GaAs laser light in KTP waveguides, electronic and optoelectronic neural network hardware and most recently image reconstruction for medical optical tomography. tomography. He has contributed to the many of the experimental work in these areas. daerah. He has over 50 publications and holds over 10 patents on these topics. MB van der Mark was born in Zuidoostbeemster, The Netherlands, on August 28, 1960. In 1985, he received the M.Sc. degree in physics ( cum laude ) followed in 1990 by the Ph.D. degree, both from the University of Amsterdam, The Netherlands. The subjects covered included nonlinear optics in fibers and coherent backscattering from highly turbid media. Since 1990, he has been with Philips Research Laboratories where he has been doing in research on acoustics, switching of ferro-electric memories, very high bit-rate telecommunication. Currently, he is a senior scientist, working on optical mammography and foundations of physics. GW't Hooft has studied physics at the University of Leiden, The Netherlands and received the Ph.D. degree in 1978. In 1979, he joined Philips Research Laboratories. Laboratorium. Since then, he has worked on various topics: viz., transport and luminescence properties of IIIV compounds, development of (ultra-)fast lasers and time-resolved optoelectonic characterisation methods. ods. His more recent research includes optical mammography and lasing of polymers. He holds a part time professorship at the University of Leiden. JH Hoogenraad received the Ph.D. degree in gelar physics in 1996 from the University of Amsterdam, The Netherlands. Belanda. He has worked on the control and reconstruction software for optical mammography at Philips Research Laboratories from 1996 till 1998. Currently, Saat ini, he is system engineer at ASML Special Applications, responsible for the overall design of advanced

lithographic equipment. ES van der Linden is a radiologist at the University Hospital in Maastricht, The Netherlands. Belanda. After medical school he did his residency for practical medical experience in the surgical department of the Hospital of Sittart (NL). In 1983, he started his training on Radiology at the Radiology Department of the University of Maastricht. In 1987, he attended a one year program on Clinical Epidemiology at the Mc Master University in Hamilton, Ontario, Canada. Kanada. After that, he became a member of the staff of the Radiology Department in Maastricht. His research was directed primarily towards the quantification of contrast enhancement in the malignancies of the breast with Magnetic Resonance Imaging. More recently he was also appointed to take over managerial work, in addition to his tasks as a radiologist to in the hospital. One of the research topics he has been pursuing during the last few years is on the evaluation of optical methods in detecting breast anomalies. Frans A. Kuijpers born in 1941. He studied applied physics at the Technical University of Delft where he graduated in 1965. After fulfilling his military service, he joined Philips Research Laboratories in 1967. His work on the absorption of hydrogen in certain intermetallic compounds resulted in the Ph.D. degree in 1973. Thereafter, he joined a research team that studied the application of magnetic bubbles in memory chips. In 1976, he was asked to become a member of the Bureau that supports the coordination of the international Philips Research. In 1979, he joined Philips Medical Systems, Best, The Netherlands, where he started in the development of ultrasound as a scientific coordinator, but also managed the realization of a linear array transducer. transducer. In 1981, he moved to the upcoming MRI field and became the project leader of the first series of MRI scanners. From 1984 till 1990, he led the Physics Department in the MR Development. In 1991, he became Research and Patent coordinator of Philips Medical Systems. This Corporate Staff function covers a number of areas, including the evaluation of emerging technologies for medical imaging. He became actively involved in the research project that studied various optical imaging methods and that resulted in the construction of the optical mammograph.