The Future of Cancer Imaging

Conventional (anatomical, structural) imaging is insensitive to the presence of cancer, often failing to yield the very information needed for accurate diagnosis and staging, for proper treatment selection and monitoring or for effective follow-up after treatment. This, fortunately, is changing. Newer techniques, already in clinical testing, are rapidly pushing clinical imaging in the same direction as the rest of medicine: away from simple detection of the gross structural end-effects of disease, and toward a patient-specific approach based on physiologic, histologic, antigenic, molecular, and (ultimately) genetic markers of disease. By 2010, unimodal, nonspecific, and insensitive radiological images may look as primitive to us as the first Roentgen radiographs. In some cases, these new scans will be so seamlessly integrated into therapeutic treatment that they may not even be thought of as imaging per se. This chapter looks forward to see how imaging for oncology may look in the coming decade, focusing upon near-term trends and techniques by selecting those already demonstrated in vivo in at least animals or which are now under human study, and thus which have moved far enough that they have already begun to impact patient care, or are likely to begin do so in the near future.

[1]  Wolfhard Semmler,et al.  Macromolecular Contrast Agents for Optical Imaging of Tumors: Comparison of Indotricarbocyanine-labeled Human Serum Albumin and Transferrin¶ , 2000, Photochemistry and photobiology.

[2]  P. Ell,et al.  The clinical application of positron emission tomography to colorectal cancer management. , 2001, The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology.

[3]  R. Blasberg,et al.  Imaging the expression of transfected genes in vivo. , 1995, Cancer research.

[4]  P. Carroll,et al.  Three-dimensional H-1 MR spectroscopic imaging of the in situ human prostate with high (0.24-0.7-cm3) spatial resolution. , 1996, Radiology.

[5]  J. Bading,et al.  Preclinical evaluation of the penciclovir analog 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine for in vivo measurement of suicide gene expression with PET. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  M J Paulus,et al.  High resolution X-ray computed tomography: an emerging tool for small animal cancer research. , 2000, Neoplasia.

[7]  R Richards-Kortum,et al.  Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications. , 2001, Journal of biomedical optics.

[8]  U. Haberkorn,et al.  PET imaging of somatostatin receptors using [68GA]DOTA-D-Phe1-Tyr3-octreotide: first results in patients with meningiomas. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[9]  A H Hielscher,et al.  Evidence of intrinsic differences in the light scattering properties of tumorigenic and nontumorigenic cells , 1998, Cancer.

[10]  M. Edreira,et al.  In vivo evaluation of three different 99mTc-labelled radiopharmaceuticals for sentinel lymph node identification , 2001, Nuclear medicine communications.

[11]  K Svanberg,et al.  Clinical multi-colour fluorescence imaging of malignant tumours - initial experience , 1998, Acta radiologica.

[12]  R Weissleder,et al.  MR imaging and scintigraphy of gene expression through melanin induction. , 1997, Radiology.

[13]  M. Phelps,et al.  PET: the merging of biology and imaging into molecular imaging. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[14]  D. Reintgen,et al.  The Use of Intraoperative Radiolymphoscintigraphy for Sentinel Node Biopsy in Patients with Malignant Melanoma , 1996, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[15]  K. Badani,et al.  Prospective evaluation of endorectal magnetic resonance imaging to detect tumor foci in men with prior negative prostastic biopsy: a pilot study. , 2000, The Journal of urology.

[16]  A. Bischof Delaloye,et al.  Tumor imaging with monoclonal antibodies. , 1995, Seminars in nuclear medicine.

[17]  P. Dieppe,et al.  Identification of pathological mineral deposits by Raman microscopy , 1991, The Lancet.

[18]  R Weissleder,et al.  In vivo imaging of proteolytic enzyme activity using a novel molecular reporter. , 2000, Cancer research.

[19]  P. Malmström,et al.  Quantitative 201Tl SPET imaging in the follow-up of treatment for brain tumour: A sensitive tool for the early identification of response to chemotherapy? , 2000, Nuclear medicine communications.

[20]  R Cubeddu,et al.  Fluorescence Lifetime Imaging of Experimental Tumors in Hematoporphyrin Derivative‐Sensitized Mice , 1997, Photochemistry and photobiology.

[21]  L Burke,et al.  Identification of cervical intraepithelial neoplasia (CIN) using UV‐excited fluorescence and diffuse‐reflectance tissue spectroscopy , 2001, Lasers in surgery and medicine.

[22]  Ralph Weissleder,et al.  Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice. , 2002, Gastroenterology.

[23]  R. Davis,et al.  In vivo detection and imaging of phosphatidylserine expression during programmed cell death. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[24]  C. Contag,et al.  Bioluminescence imaging of lymphocyte trafficking in vivo. , 2001, Experimental hematology.

[25]  A. Kleinschmidt,et al.  Noninvasive Functional Imaging of Human Brain Using Light , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  E. Marshall Rival Genome Sequencers Celebrate a Milestone Together , 2000, Science.

[27]  O. Hoekstra,et al.  Systematic review of the diagnostic accuracy of 18F‐fluorodeoxyglucose positron emission tomography in melanoma patients , 2001 .

[28]  T. Shiga,et al.  Electron spin relaxation of synthetic melanin and melanin-containing human tissues as studied by electron spin echo and electron spin resonance. , 1985, Archives of biochemistry and biophysics.

[29]  R K Babayan,et al.  Implications of prostate micrometastases in pelvic lymph nodes: an archival tissue study. , 1996, Urology.

[30]  R L Wahl,et al.  Metastases from non-small cell lung cancer: mediastinal staging in the 1990s--meta-analytic comparison of PET and CT. , 1999, Radiology.

[31]  R L Somorjai,et al.  The classification of benign and malignant human prostate tissue by multivariate analysis of 1H magnetic resonance spectra. , 1997, Cancer research.

[32]  C. Claussen,et al.  Early prediction of treatment response to high-dose salvage chemotherapy in patients with relapsed germ cell cancer using [18F]FDG PET , 2002, British Journal of Cancer.

[33]  M. Graham,et al.  Can FDG-PET reduce the need for mediastinoscopy in potentially resectable nonsmall cell lung cancer? , 2002, The Annals of thoracic surgery.

[34]  Yang Cr,et al.  Unsuspected Prostate Carcinoma and Prostatic Intraepithelial Neoplasm in Taiwanese Patients Undergoing Cystoprostatectomy. , 1999 .

[35]  E. Shoubridge,et al.  Proton and phosphorus magnetic resonance spectroscopy of human astrocytomas in vivo. Preliminary observations on tumor grading , 1990, NMR in biomedicine.

[36]  J. Saunders,et al.  Classification of Brain Tumors by Ex Vivo 1H NMR Spectroscopy , 1995, Journal of neurochemistry.

[37]  P. Carroll,et al.  Prostate cancer: localization with three-dimensional proton MR spectroscopic imaging--clinicopathologic study. , 1999, Radiology.

[38]  M. Cotten,et al.  Receptor-mediated transport of DNA into eukaryotic cells. , 1993, Methods in enzymology.

[39]  B. Goins,et al.  Use of (99m)Tc-labeled liposomes encapsulating blue dye for identification of the sentinel lymph node. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[40]  S. Cummings,et al.  Continuing screening mammography in women aged 70 to 79 years: impact on life expectancy and cost-effectiveness. , 1999, JAMA.

[41]  S. Feig Current status of screening mammography. , 2002, Obstetrics and gynecology clinics of North America.

[42]  J. Coyle,et al.  Immunocytochemical localization of N-acetyl-aspartate with monoclonal antibodies , 1991, Neuroscience.

[43]  R Weissleder,et al.  Measuring transferrin receptor gene expression by NMR imaging. , 1998, Biochimica et biophysica acta.

[44]  R. Wahl,et al.  Prospective evaluation of 2-[18F]-2-deoxy-D-glucose positron emission tomography in staging of regional lymph nodes in patients with cutaneous malignant melanoma. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[45]  T J Flotte,et al.  Ultraviolet laser‐induced fluorescence of colonic tissue: Basic biology and diagnostic potential , 1992, Lasers in surgery and medicine.

[46]  R L Somorjai,et al.  Magnetic resonance spectroscopy of the malignant prostate gland after radiotherapy: a histopathologic study of diagnostic validity. , 2001, International journal of radiation oncology, biology, physics.

[47]  S. Larson,et al.  Imaging transgene expression with radionuclide imaging technologies. , 2000, Neoplasia.

[48]  David K. Stevenson,et al.  Tissue Optics , 1997, Science.

[49]  B. Maliwal,et al.  Frequency‐domain fluorescence microscopy with the LED as a light source , 2001, Journal of microscopy.

[50]  K. Badizadegan,et al.  NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes. , 2002, Cancer research.

[51]  J. Fujimoto,et al.  In vivo endoscopic optical biopsy with optical coherence tomography. , 1997, Science.

[52]  M. Banerjee,et al.  Prognostic implications of a positive apical margin in radical prostatectomy specimens. , 1998, The Journal of urology.

[53]  R. Foster,et al.  The sentinel node in breast cancer--a multicenter validation study. , 1998, The New England journal of medicine.

[54]  R Weissleder,et al.  Preparation of a cathepsin D sensitive near-infrared fluorescence probe for imaging. , 1999, Bioconjugate chemistry.

[55]  J. Schneider-Mergener,et al.  Cyanine Dye Labeled Vasoactive Intestinal Peptide and Somatostatin Analog for Optical Detection of Gastroenteropancreatic Tumors , 2000, Annals of the New York Academy of Sciences.

[56]  P. Marsden,et al.  Whole-body 18F-fluorodeoxyglucose positron emission tomography in preoperative evaluation of lung cancer , 1994, The Lancet.

[57]  I J Bigio,et al.  Non-invasive measurement of chemotherapy drug concentrations in tissue: preliminary demonstrations of in vivo measurements. , 1999, Physics in medicine and biology.

[58]  L. Hughes,et al.  FAILURE OF TETRACHLORODECAOXYGEN ANION COMPLEX TO ASSIST WOUND HEALING , 1989, The Lancet.

[59]  Gert W. t'Hooft,et al.  First results from the Philips optical mammoscope , 1998, European Conference on Biomedical Optics.

[60]  G. Johnson,et al.  Magnetic resonance microscopy of mouse embryos. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[61]  S A Boppart,et al.  High resolution imaging of transitional cell carcinoma with optical coherence tomography: feasibility for the evaluation of bladder pathology. , 1999, The British journal of radiology.

[62]  B. Goins,et al.  Use of 99mTc-Labeled Liposomes Encapsulating Blue Dye for Identification of the Sentinel Lymph Node , 2001 .

[63]  D. Weaver,et al.  Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. , 1993, Surgical oncology.

[64]  Thomas E Merchant,et al.  Malignant breast tumor phospholipid profiles using (31)P magnetic resonance. , 2002, Cancer letters.

[65]  R K Jain,et al.  A method for labeling cells for positron emission tomography (PET) studies. , 1994, Journal of immunological methods.

[66]  E. Sevick-Muraca,et al.  Measurements of Multiply Scattered Light for On‐Line Monitoring of Changes in Size Distribution of Cell Debris Suspension , 1999, Biotechnology progress.

[67]  R R Alfano,et al.  In vivo native cellular fluorescence and histological characteristics of head and neck cancer. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[68]  S Nioka,et al.  Time-resolved spectroscopy of hemoglobin and myoglobin in resting and ischemic muscle. , 1988, Analytical biochemistry.

[69]  M. Greco,et al.  Nuclear medicine approaches for detection of axillary lymph node metastases. , 1998, The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology.

[70]  Ming Zhao,et al.  Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent , 2001, Nature Medicine.

[71]  K Svanberg,et al.  In vivo fluorescence imaging for tissue diagnostics. , 1997, Physics in medicine and biology.

[72]  J Beuthan,et al.  The spatial variation of the refractive index in biological cells. , 1996, Physics in medicine and biology.

[73]  K Svanberg,et al.  Preliminary evaluation of two fluorescence imaging methods for the detection and the delineation of basal cell carcinomas of the skin , 2000, Lasers in surgery and medicine.

[74]  R. Rava,et al.  In situ optical histochemistry of human artery using near infrared Fourier transform Raman spectroscopy. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[75]  E R Anderson,et al.  Frequency-domain photon migration measurements of normal and malignant tissue optical properties in a human subject. , 1997, Applied optics.

[76]  Judith R. Mourant,et al.  Light scattering from cells: the contribution of the nucleus and the effects of proliferative status , 2000 .

[77]  M W Vannier,et al.  Multispectral analysis of MR images of the breast. , 1987, Radiology.

[78]  P. Thimister,et al.  In vivo detection of apoptosis in an intracardiac tumor. , 2001, JAMA.

[79]  H. Barr,et al.  Raman Spectroscopy for Early Detection of Laryngeal Malignancy: Preliminary Results , 2000, The Laryngoscope.

[80]  Michael S. Feld,et al.  Polarized light scattering spectroscopy for quantitative measurement of epithelial cellular structures in situ , 1999 .

[81]  J. Mullins,et al.  Photonic detection of bacterial pathogens in living hosts , 1995, Molecular microbiology.

[82]  C. Miller,et al.  Meta-analysis of sentinel lymph node biopsy in breast cancer. , 1999, The Journal of surgical research.

[83]  D. Bornhop,et al.  Fluorescent tissue site-selective lanthanide chelate, Tb-PCTMB for enhanced imaging of cancer. , 1999, Analytical chemistry.

[84]  Susan M. Chang,et al.  Three-dimensional magnetic resonance spectroscopic imaging of histologically confirmed brain tumors. , 2001, Magnetic resonance imaging.

[85]  C K Hoh,et al.  A synthetic macromolecule for sentinel node detection: (99m)Tc-DTPA-mannosyl-dextran. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[86]  E. Ryding,et al.  201Thallium SPECT and 1H-MRS Compared with MRI in Chemotherapy Monitoring of High-grade Malignant Astrocytomas , 2004, Journal of Neuro-Oncology.

[87]  D. Leibfritz,et al.  Pre-operative localized in vivo proton spectroscopy in cerebral tumors at 4.0 Tesla--first results. , 1989, Magnetic resonance imaging.

[88]  W. Ellis,et al.  Repeat prostate needle biopsy: who needs it? , 1995, The Journal of urology.

[89]  Michael S. Feld,et al.  Imaging human epithelial properties with polarized light-scattering spectroscopy , 2001, Nature Medicine.

[90]  C. J. Rosenquist,et al.  Screening mammography beginning at age 40 years , 1998, Cancer.

[91]  S. Heywang-Köbrunner,et al.  [Optical mammography in preoperative patients]. , 1998, Aktuelle Radiologie.

[92]  B. Conklin,et al.  Engineering receptors activated solely by synthetic ligands (RASSLs). , 2001, Trends in pharmacological sciences.

[93]  P. Lind,et al.  Probe-guided surgery for colorectal cancer. , 2000, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.

[94]  B. Beauvoit,et al.  Correlation between the light scattering and the mitochondrial content of normal tissues and transplantable rodent tumors. , 1995, Analytical biochemistry.

[95]  T. Powles,et al.  DETECTION OF MICROMETASTASES IN PATIENTS WITH PRIMARY BREAST CANCER , 1983, The Lancet.

[96]  B E Bouma,et al.  Diagnosis of specialized intestinal metaplasia by optical coherence tomography. , 2001, Gastroenterology.

[97]  V. Ntziachristos,et al.  Hydrophilic Cyanine Dyes as Contrast Agents for Near-infrared Tumor Imaging: Synthesis, Photophysical Properties and Spectroscopic In vivo Characterization¶ , 2000, Photochemistry and photobiology.

[98]  R Weissleder,et al.  Near-infrared optical imaging of protease activity for tumor detection. , 1999, Radiology.

[99]  J. Kronauge,et al.  Effect of mitochondrial and plasma membrane potentials on accumulation of hexakis (2-methoxyisobutylisonitrile) technetium(I) in cultured mouse fibroblasts. , 1990, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[100]  R Weissleder,et al.  Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging. , 2001, Bioconjugate chemistry.

[101]  J. Bruner,et al.  Use of [18F]fluorodeoxyglucose positron emission tomography in patients with primary malignant brain tumors , 1993, Annals of neurology.

[102]  R. Franklin,et al.  The Intermediary Metabolism of the Prostate: A Key to Understanding the Pathogenesis and Progression of Prostate Malignancy , 2000, Oncology.

[103]  Richard A. Falk,et al.  Who Needs It , 1975 .

[104]  J. Roodenburg,et al.  In vivo detection of dysplastic tissue by Raman spectroscopy. , 2000, Analytical chemistry.

[105]  Decision analysis for the cost effectiveness of sestamibi scintimammography in minimizing unnecessary biopsies. , 2000, The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology.

[106]  J. J. Coleman,et al.  Initial assessment of positron emission tomography for detection of nonpalpable regional lymphatic metastases in melanoma , 1997, Journal of surgical oncology.

[107]  J. Kurhanewicz,et al.  Magnetic resonance imaging and spectroscopic imaging: Improved patient selection and potential for metabolic intermediate endpoints in prostate cancer chemoprevention trials. , 2001, Urology.

[108]  H. Sweeney,et al.  Noninvasive measurement of gene expression in skeletal muscle. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[109]  A E Giuliano,et al.  Sentinel lymphadenectomy in breast cancer. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[110]  R. N. Goble,et al.  Performance evaluation of the microPET P4: a PET system dedicated to animal imaging. , 2001, Physics in medicine and biology.

[111]  P. Narayan,et al.  Citrate in the diagnosis of prostate cancer , 1999, The Prostate.

[112]  N Sailasuta,et al.  Single‐voxel oversampled J‐resolved spectroscopy of in vivo human prostate tissue , 2001, Magnetic resonance in medicine.

[113]  W. Fair,et al.  Prostate‐specific membrane antigen , 1997, The Prostate.

[114]  Sharon Thomsen,et al.  Spectroscopic diagnosis of cervical intraepithelial neoplasia (CIN) in vivo using laser‐induced fluorescence spectra at multiple excitation wavlengths , 1996, Lasers in surgery and medicine.

[115]  R. Turner,et al.  Carbon dye as an adjunct to isosulfan blue dye for sentinel lymph node dissection. , 1999, Surgery.

[116]  T. Liu,et al.  Video microscopy of tumor metastasis: using the green fluorescent protein (GFP) gene as a cancer-cell-labeling system , 1999, Clinical & Experimental Metastasis.

[117]  P. Lam Minimal-access surgery for staging of malignant melanoma , 1996 .

[118]  J. Tisnado,et al.  Use of isosulfan blue for identification of lymphatic vessels: experimental and clinical evaluation. , 1982, AJR. American journal of roentgenology.

[119]  D A Benaron,et al.  Optical time-of-flight and absorbance imaging of biologic media. , 1993, Science.

[120]  J. Nicolas Applications of low-light imaging to life sciences. , 1994, Journal of bioluminescence and chemiluminescence.

[121]  P. Rüegsegger,et al.  Morphometric analysis of human bone biopsies: a quantitative structural comparison of histological sections and micro-computed tomography. , 1998, Bone.

[122]  P Armstrong,et al.  Staging non-small cell lung cancer. , 1993, Clinical radiology.

[123]  R. Rainsbury,et al.  Detection of residual disease following breast‐conserving surgery , 1998, The British journal of surgery.

[124]  J R Griffiths,et al.  Monitoring pharmacokinetics of anticancer drugs: non-invasive investigation using magnetic resonance spectroscopy. , 2000, Advanced drug delivery reviews.

[125]  M. Kattan,et al.  Risk factors for urinary incontinence after radical prostatectomy. , 1996, The Journal of urology.

[126]  C. Pozzilli,et al.  TRACKING OF INDIUM‐111‐OXINE LABELLED LYMPHOCYTES IN AUTOIMMUNE THYROID DISEASE , 1983, Clinical endocrinology.

[127]  R. Rava,et al.  Quantitative histochemical analysis of human artery using Raman spectroscopy. , 1992, Journal of photochemistry and photobiology. B, Biology.

[128]  Anna Moore,et al.  In vivo magnetic resonance imaging of transgene expression , 2000, Nature Medicine.

[129]  F. Berger,et al.  Breast imaging technology: Recent advances in imaging endogenous or transferred gene expression utilizing radionuclide technologies in living subjects - applications to breast cancer , 2000, Breast Cancer Research.

[130]  K. Seung,et al.  Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. , 2002, Journal of the American College of Cardiology.

[131]  J Humm,et al.  Imaging transcriptional regulation of p53-dependent genes with positron emission tomography in vivo , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[132]  Meng Yang,et al.  Direct external imaging of nascent cancer, tumor progression, angiogenesis, and metastasis on internal organs in the fluorescent orthotopic model , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[133]  N. Petrelli,et al.  Clinical utility of external immunoscintigraphy with the IMMU-4 technetium-99m Fab' antibody fragment in patients undergoing surgery for carcinoma of the colon and rectum: results of a pivotal, phase III trial. The Immunomedics Study Group. , 1996, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[134]  S. Cherry,et al.  Performance evaluation of microPET: a high-resolution lutetium oxyorthosilicate PET scanner for animal imaging. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[135]  B. Tromberg,et al.  Spectroscopy enhances the information content of optical mammography. , 2002, Journal of biomedical optics.

[136]  D. Boas,et al.  Bedside functional imaging of the premature infant brain during passive motor activation , 1999, Photonics West - Biomedical Optics.

[137]  J. Doppman,et al.  Value of somatostatin receptor scintigraphy: a prospective study in gastrinoma of its effect on clinical management. , 1997, Gastroenterology.

[138]  R. Hustinx,et al.  Staging of non-small-cell lung cancer by whole-body fluorine-18 deoxyglucose positron emission tomography , 1996, European Journal of Nuclear Medicine.

[139]  M. Terris,et al.  Efficacy of transrectal ultrasound for identification of clinically undetected prostate cancer. , 1991, The Journal of urology.

[140]  D A Benaron,et al.  Imaging transgenic animals. , 1999, Annual review of biomedical engineering.

[141]  R. Stahel,et al.  Detection of bone marrow metastasis in small-cell lung cancer by monoclonal antibody. , 1985, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[142]  S. Gambhir,et al.  Optical imaging of Renilla luciferase reporter gene expression in living mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[143]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[144]  F. Hartveit,et al.  Clinically undiagnosed malignant tumours found at autopsy , 1990, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[145]  R E Jacobs,et al.  Looking deeper into vertebrate development. , 1999, Trends in cell biology.

[146]  S. Achilefu,et al.  Novel receptor-targeted fluorescent contrast agents for in vivo tumor imaging. , 2000, Investigative radiology.

[147]  R Weissleder,et al.  In vivo imaging of gene expression:. , 2001, Academic radiology.

[148]  J. Mourant,et al.  Noninvasive, in-situ measurement of drug concentrations in tissue using optical spectroscopy. , 1999, Journal of gravitational physiology : a journal of the International Society for Gravitational Physiology.

[149]  F. Blankenberg,et al.  Imaging cyclophosphamide-induced intramedullary apoptosis in rats using 99mTc-radiolabeled annexin V. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[150]  A. Cesinaro,et al.  Endorectal coil MRI in local staging of rectal cancer. , 2002, La Radiologia medica.

[151]  K. Pienta,et al.  Identification of nuclear matrix proteins in the cancer and normal rat prostate. , 1991, Cancer research.

[152]  J. S. Reynolds,et al.  Imaging of Spontaneous Canine Mammary Tumors Using Fluorescent Contrast Agents , 1999, Photochemistry and photobiology.

[153]  A. Cesinaro,et al.  [Magnetic resonance with endorectal coil in the local staging of prostatic carcinoma. Comparison with histologic macrosections in 40 cases]. , 1999, La Radiologia medica.

[154]  J. Fujimoto,et al.  Optical coherence tomography: advanced technology for the endoscopic imaging of Barrett's esophagus. , 2000, Endoscopy.

[155]  R Weissleder,et al.  Magnetically labeled cells can be detected by MR imaging , 1997, Journal of magnetic resonance imaging : JMRI.

[156]  S. H. Koenig,et al.  Sources of the increased longitudinal relaxation rates observed in melanotic melanoma. An in vitro study of synthetic melanins. , 1989, Investigative radiology.

[157]  D L Morton,et al.  Technical details of intraoperative lymphatic mapping for early stage melanoma. , 1992, Archives of surgery.

[158]  A. Folpe,et al.  (F-18) fluorodeoxyglucose positron emission tomography as a predictor of pathologic grade and other prognostic variables in bone and soft tissue sarcoma. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[159]  N. Satyamurthy,et al.  Noninvasive, quantitative imaging in living animals of a mutant dopamine D2 receptor reporter gene in which ligand binding is uncoupled from signal transduction , 2001, Gene Therapy.

[160]  V. Speights,et al.  The incidence of unsuspected metastases from clinically benign prostate glands with latent prostate carcinoma. , 1995, Archives of pathology & laboratory medicine.

[161]  A. Eberle,et al.  Receptor targeting for tumor localisation and therapy with radiopeptides. , 2000, Current medicinal chemistry.

[162]  G. Poli,et al.  In situ determination by surface chemiluminescence of temporal relationships between evolving warm ischemia‐reperfusion injury in rat liver and phagocyte activation and recruitment , 2000, Hepatology.

[163]  J Kurhanewicz,et al.  The prostate: MR imaging and spectroscopy. Present and future. , 2000 .

[164]  Siavash Yazdanfar,et al.  Real-time in vivo color Doppler optical coherence tomography. , 2002, Journal of biomedical optics.

[165]  B. Chance,et al.  Cognition-activated low-frequency modulation of light absorption in human brain. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[166]  C. Contag,et al.  Noninvasive assessment of tumor cell proliferation in animal models. , 1999, Neoplasia.

[167]  D L Farkas,et al.  Detection of tumorigenesis in rat bladders with optical coherence tomography. , 2001, Medical physics.

[168]  D. Krag Why perform randomized clinical trials for sentinel node surgery for breast cancer? , 2001, American journal of surgery.

[169]  A. Alavi,et al.  Imaging in vivo herpes simplex virus thymidine kinase gene transfer to tumour-bearing rodents using positron emission tomography and [18F]FHPG , 2001, European Journal of Nuclear Medicine.

[170]  J Kotzerke,et al.  Lymphoma: role of whole-body 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) PET in nodal staging. , 1997, Radiology.

[171]  F Regan,et al.  Indium-111 capromab pendetide (ProstaScint) imaging to detect recurrent and metastatic prostate cancer. , 1998, Clinical nuclear medicine.

[172]  D. Boas,et al.  J. Perinat. Med. Bedside functional imaging of the premature infant brain 29 (2001) 3352343 during passive motor activation , 2001 .

[173]  M. Soloway,et al.  Induction androgen deprivation therapy before radical prostatectomy for prostate cancer--initial results. , 1996, British journal of urology.

[174]  R K Jain,et al.  Physiological barriers to delivery of monoclonal antibodies and other macromolecules in tumors. , 1990, Cancer research.

[175]  D A Benaron,et al.  Imaging brain structure and function, infection and gene expression in the body using light. , 1997, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[176]  D. Krag,et al.  Gamma-probe guided localization of lymph nodes. , 1993, Surgical oncology.

[177]  Irene Georgakoudi,et al.  Trimodal spectroscopy for the detection and characterization of cervical precancers in vivo. , 2002, American journal of obstetrics and gynecology.

[178]  B. Chance Near-infrared (NIR) optical spectroscopy characterizes breast tissue hormonal and age status. , 2001, Academic radiology.

[179]  Cedric Yu,et al.  Magnetic resonance spectroscopic imaging-guided brachytherapy for localized prostate cancer. , 2001, International journal of radiation oncology, biology, physics.

[180]  W. Catalona,et al.  Serial prostatic biopsies in men with persistently elevated serum prostate specific antigen values. , 1994, The Journal of urology.

[181]  G Friedmann,et al.  Human brain tumors: spectral patterns detected with localized H-1 MR spectroscopy. , 1992, Radiology.

[182]  R. Jain,et al.  Intracellular magnetic labeling of lymphocytes for in vivo trafficking studies. , 1998, BioTechniques.

[183]  Gregory W. Faris,et al.  Spectroscopic properties of upconverting phosphor reporters , 1999, Photonics West - Biomedical Optics.

[184]  G. Banting,et al.  TGN38-green fluorescent protein hybrid proteins expressed in stably transfected eukaryotic cells provide a tool for the real-time, in vivo study of membrane traffic pathways and suggest a possible role for ratTGN38. , 1996, Journal of cell science.

[185]  E. Sevick-Muraca,et al.  Measurement of particle-size distribution and volume fraction in concentrated suspensions with photon migration techniques. , 1997, Applied optics.

[186]  S. Achilefu,et al.  Novel fluorescent contrast agents for optical imaging of in vivo tumors based on a receptor-targeted dye-peptide conjugate platform. , 2001, Journal of biomedical optics.

[187]  J. Leonard,et al.  Comparison of fluorine‐18 fluorodeoxyglucose positron emission tomography and Ga‐67 scintigraphy in evaluation of lymphoma , 2002, Cancer.

[188]  E. Gratton,et al.  Cerebral and muscle oxygen saturation measurement by frequency-domain near-infra-red spectrometer , 1995, Medical and Biological Engineering and Computing.

[189]  A. Luini,et al.  Optimized sentinel node scintigraphy in breast cancer. , 1998, The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology.

[190]  J. Barrio,et al.  Monitoring gene therapy with reporter gene imaging. , 2001, Seminars in nuclear medicine.

[191]  D. Weaver,et al.  Gamma-probe-guided lymph node localization in malignant melanoma. , 1993, Surgical oncology.

[192]  V. Quaresima,et al.  Calf and shin muscle oxygenation patterns and femoral artery blood flow during dynamic plantar flexion exercise in humans , 2001, European Journal of Applied Physiology.

[193]  A. Villringer,et al.  Global Cerebral Ischemia in the Rat: Online Monitoring of Oxygen Free Radical Production Using Chemiluminescence in vivo , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[194]  C. Roehrborn,et al.  Diagnostic yield of repeated transrectal ultrasound-guided biopsies stratified by specific histopathologic diagnoses and prostate specific antigen levels. , 1996, Urology.

[195]  J. Glickson,et al.  Proton nuclear magnetic resonances study of bleomycin in aqueous solution. Assignment of resonances. , 1977, Biochemistry.

[196]  D. Tindall,et al.  Hormonal regulation of prostate-specific antigen messenger RNA in human prostatic adenocarcinoma cell line LNCaP. , 1991, Cancer research.

[197]  J. Glickson Clinical NMR Spectroscopy of Tumors: Current Status and Future Directions , 1989, Investigative radiology.

[198]  H. Huland,et al.  Systematic sextant biopsies in 651 patients referred for prostate evaluation. , 1994, The Journal of urology.

[199]  J. Barrio,et al.  Human pharmacokinetic and dosimetry studies of [(18)F]FHBG: a reporter probe for imaging herpes simplex virus type-1 thymidine kinase reporter gene expression. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[200]  David M. Otten,et al.  Automated quantitation of tissue components using real-time spectroscopy , 1998, European Conference on Biomedical Optics.

[201]  Muscle oxygenation by fast near infrared spectrophotometry (NIRS) in ischemic forearm. , 1992, Advances in experimental medicine and biology.

[202]  A. C. Bird,et al.  Optical Coherence Tomography (OCT): principles of operation, technology, indications in vitreoretinal imaging and interpretation of results , 2004, International Ophthalmology.

[203]  W. Semmler,et al.  Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands , 2001, Nature Biotechnology.

[204]  H. Kuwano,et al.  Comparison between positron emission tomography and computed tomography in the use of the assessment of esophageal carcinoma , 2002, Cancer.

[205]  H. Sakahara,et al.  Establishment and characterization of a breast cancer cell line expressing Na+/I- symporters for radioiodide concentrator gene therapy. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[206]  Scott E. Fraser,et al.  In vivo visualization of gene expression using magnetic resonance imaging , 2000, Nature Biotechnology.

[207]  J. Schuman,et al.  Optical coherence tomography. , 2000, Science.

[208]  M E Phelps,et al.  Positron emission tomography provides molecular imaging of biological processes. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[209]  E. Pennisi Finally, the Book of Life and Instructions for Navigating It , 2000, Science.

[210]  R. Jain,et al.  Imaging of activated natural killer cells in mice by positron emission tomography: preferential uptake in tumors. , 1993, Cancer research.

[211]  A. J. Kumar,et al.  Intracranial metastatic melanoma: correlation between MR imaging characteristics and melanin content. , 1995, AJR. American journal of roentgenology.

[212]  Eva M. Sevick-Muraca,et al.  Pharmacokinetics of ICG and HPPH-car for the Detection of Normal and Tumor Tissue Using Fluorescence, Near-infrared Reflectance Imaging: A Case Study¶ , 2000, Photochemistry and photobiology.

[213]  R Weissleder,et al.  Glossary of molecular imaging terminology. , 2001, Academic radiology.

[214]  David K. Stevenson,et al.  Automated classification of tissue by type using real-time spectroscopy , 1998 .

[215]  D A Benaron,et al.  Tissue Optics , 1997, Science.

[216]  Albert Cerussi,et al.  Noninvasive functional optical spectroscopy of human breast tissue , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[217]  M. Torchia,et al.  Interstitial MR lymphangiography for the detection of sentinel lymph nodes , 2001, Journal of surgical oncology.

[218]  H. Moch,et al.  Selective Axillary Surgery in Breast Cancer Patients Based on Positron Emission Tomography with 18F-Fluoro-2-Deoxy-D-Glucose: not Yet! , 2004, Breast Cancer Research and Treatment.

[219]  T. Irimura,et al.  Real-time PET analysis of metastatic tumor cell trafficking in vivo and its relation to adhesion properties. , 1995, Biochimica et biophysica acta.

[220]  Daniel L. Farkas,et al.  Tumor labeling in vivo using cyanine-conjugated monoclonal antibodies , 1995, Cancer Immunology, Immunotherapy.

[221]  R. Ghossein,et al.  Molecular detection and characterisation of circulating tumour cells and micrometastases in solid tumours. , 2000, European journal of cancer.

[222]  E F Halpern,et al.  Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings. , 1994, Radiology.

[223]  C Van Ongeval,et al.  Localized 1H NMR spectroscopy in fifty cases of newly diagnosed intracranial tumors. , 1991, Journal of computer assisted tomography.

[224]  Daniel J. Hawrysz,et al.  Developments toward diagnostic breast cancer imaging using near-infrared optical measurements and fluorescent contrast agents. , 2000, Neoplasia.

[225]  J. Frahm,et al.  Noninvasive differentiation of tumors with use of localized H-1 MR spectroscopy in vivo: initial experience in patients with cerebral tumors. , 1989, Radiology.

[226]  R. Glasspool,et al.  Clinical imaging of cancer metastasis. , 2000, European journal of cancer.