Maryann Fitzmaurice M.D., Ph.D.

Senior Research Associate
Adjunct Associate Professor

Mailing Address:
2103 Cornell Rd.
WRB 6542
Cleveland, OH 44106-7288

phone: (216) 368-0011
fax: (216) 368-1539
email: Maryann.Fitzmaurice@Case.edu

Biography

1973 B.S. in Biochemistry, with Distinction, Iowa State University, Ames, IA
1974-1978 National Institutes of Health-National Graduate Medical Sciences Traineeship, Department of Pathology, Case Western Reserve University, Cleveland, OH
1982 Ph.D. in Experimental pathology, Department of Pathology, Case Western Reserve University, Cleveland, OH
1983 M.D., School of Medicine, Case Western Reserve University, Cleveland, OH
1983-1987 Resident in Anatomic and Clinical Pathology, Department of Pathology, Cleveland Clinic Foundation, Cleveland, OH
1987-1988 Fellow, Department of Immunopathology, Cleveland Clinic Foundation, Cleveland, OH
1988-1990 Clinical Associate, Department of Pathology, Cleveland Clinic Foundation, Cleveland, OH
1990-1991 Staff Surgical Pathologist, Department of Pathology, Henry Ford Hospital, Detroit, MI
1991-2007 Staff Surgical Pathologist and Medical Director of Immunohistochemistry Laboratory, Department of Pathology, University Hospitals of Cleveland, Cleveland, OH
1992-present Visiting Scientist, G.R. Harrison Spectroscopy Laboratory, Massachusetts Institute of Technology, Cambridge, MA
1992-2005 Assistant Professor of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH
2002-2005 Adjunct Assistant Professor of General Medical Sciences (Cancer Center), School of Medicine, Case Western Reserve University, Cleveland, OH
2005-2007 Associate Professor of Pathology and General Medical Sciences (Cancer Center), School of Medicine, Case Western Reserve University, Cleveland, OH
2007-present Senior Research Associate and Adjunct Associate Professor of Pathology and Oncology (Cancer Center), School of Medicine, Case Western Reserve University, Cleveland, OH


Research
My research interests are in the development of novel, cutting-edge technologies for in vivo real time disease diagnosis in humans using optical spectroscopy. This research is performed as part of a multi-disciplinary, multi-institutional consortium including Case Western Reserve University, The Massachusetts Institute of Technology, University Hospitals-Case Medical Center and several other academic medical centers. This consortium has done pioneering work in the field of diagnostic optical spectroscopy in which we exploit the interaction of light with tissue to render disease diagnoses, in patients, in vivo, in real time, at the bedside, without the need for tissue removal through biopsy or surgical excision. This paradigm shift from in vitro to in vivo diagnosis is becoming a pressing need in the era of minimally invasive surgery, which may ultimately render conventional diagnostic techniques obsolete. The current diagnostic targets of this research are vulnerable atherosclerotic plaque and breast cancer. A wide variety of spectroscopic techniques, including fluorescence, diffuse reflectance, light scattering and Raman scattering, are being investigated. Fluorescence and Raman microspectroscopy are used to deconvolve the tissue spectra; chemometric and modeling techniques to develop algorithms for disease diagnosis based on the spectroscopic signatures of the diseased tissue. This work has led to the creation of three clinical spectroscopy systems for real time in vivo disease diagnosis that are currently undergoing testing in a number of clinical settings at University Hospitals and other academic medical centers across the country. Two of the clinical systems are multi-modal: one combining fluorescence, diffuse reflectance and light scattering spectroscopy; and the other combining fluorescence, diffuse reflectance and Raman spectroscopy. There is also a third clinical system, a Raman spectroscopy system that is specifically designed to aid in retrieval of microcalcifications during stereotactic breast biopsy of a suspect lesion identified on mammography. The following are summaries of some of our current projects.

Raman Spectroscopy of Microcalcifications in the Diagnosis of Breast Cancer
The Raman effect was discovered in 1928 in Calcutta, India by Sir C. V. Raman, who received the Nobel Prize in Physics in 1930 [2]. It has been used widely as a tool in the physical sciences and industry, but has only recently been used in biomedical applications.

Raman spectroscopy is an inelastic scattering process in which a photon is absorbed and re-emitted at a lower energy. The difference in energy between the incident photon and the emitted photon translates into a shift in wavelength (Raman shift). There are different shifts for each molecular bond present in the tissue interrogated. This creates a fingerprint spectrum that identifies the biochemical moieties present in the tissue.

We have applied Raman spectroscopy for clinical diagnosis of a number of human diseases, including breast cancer. Microcalcifications are deposits of calcium salts within breast tissue. When seen at mammography, they localize the most significant abnormality in the breast and are therefore a target for needle biopsy. Despite stereotactic guidance, needle biopsy fails to retrieve target microcalcifications in up to 15% of patients. Raman spectroscopy uses light to obtain a chemical fingerprint of breast tissue. It is exquisitely sensitive to calcium-containing minerals and thus the presence of microcalcifications in breast tissue. As such it can be used to localize microcalcifications within breast tissue to be biopsied and distinguish type I calcium oxalate microcalcifications typically associated with benign breast lesions from type II calcium hydroxyapatite microcalcifications which may be associated with malignant breast lesions. Thus Raman spectroscopy shows promise as a clinical tool to provide real-time feedback to the radiologist to improve retrieval of microcalcifications during stereotactic breast needle biopsy.

Collaborators:
MIT: Zoya Volynskaya (Ph.D. candidate), Abigail Haka, Ph.D., Karen Shafer, Ph.D., Ramachandra Dasari, Ph.D. and Michael Feld, Ph.D. Director of George R. Harrison Spectroscopy Laboratory)

University Hospitals-Case Medical Center: Nina Klein, MD, Donna Plecha MD, Nancy Wang, MD and Wendy Liu, MD

Multi-Modal Spectroscopy Diagnosis of Vulnerable Atherosclerotic Plaque
The vast majority of acute ischemic events, such as myocardial infarction (MI) or stroke, result from the rupture of asymptomatic vulnerable atherosclerotic plaques resulting in thrombotic vascular occlusion. Most of these vulnerable plaques do not exhibit significant stenosis that can be detected by current diagnostic techniques such as coronary angiography, and therefore go untreated. The key morphologic features of vulnerable plaque are a thin fibrous cap, large necrotic core, inflammation (superficial foam cells) and acute intraplaque hemorrhage. Early detection and treatment of these rupture-prone vulnerable atherosclerotic plaques is critical to reducing patient mortality associated with cardiovascular disease.

We have combined Raman spectroscopy with intrinsic fluorescence (IFS) and diffuse reflectance (DRS) spectroscopy into a technique we term multi-modal spectroscopy (MMS).These three optical spectroscopy techniques provide complimentary information about the tissue being interrogated as they probe different tissue constituents and can probe the tissue at different depths. IFS is a technique in which the measured fluorescence spectrum is corrected for the distorting effects of tissue absorption and scattering. It can be used to determine the thickness of the fibrous cap (structural protein content). Raman and DRS spectroscopy can be used to detect the presence of a large necrotic lipid core or lipid-rich superficial foam cells (beta-carotene and cholesterol content). DRS can also be used to detect intraplaque hemorrhage (oxy- and deoxy-hemoglobin content). Thus MMS may be a powerful clinical tool to identify vulnerable plaque.

Collaborators:
MIT: Obrad Šćepanović, Ph.D., Jason Motz, Ph.D., Ramachandra Dasari, Ph.D. and Michael Feld, Ph.D.

Metro West Medical Center, Natick, MA: Arnold Miller, Ph.D.

Publications
Volynskaya Z, Haka A, Bechtel K, Fitzmaurice M, Shenk R, Wang N, Nazemi J, Dasari R and Feld M: Diagnosing breast cancer using diffuse reflectance and intrinsic fluorescence spectroscopy. J Biomed Optics 13(2): 024012, 2008. PMID: 18465975

Šćepanović OR, Fitzmaurice M, Gardecki JA, Angheloiu GO, Awasthi S, Motz JT, Kramer JR, Dasari RR and Feld MS: Detection of morphological markers of vulnerable atherosclerotic plaque using multi- modal spectroscopy. J Biomed Optics 11(2): 021007 (1-8), 2006. PMID: 16674182

Angheloiu GO, Arendt JT, Müller MG, Georgakoudi I, Haka AS, Motz JT, Šćepanović OR, Kuban BD, Myles JL, Miller F, Podrez EA, Fitzmaurice M, Kramer JR and Feld MS: Intrinsic fluorescence and diffuse reflectance spectroscopy identify superficial foam cells in coronary plaques prone to erosion. Arteriosclerosis, Thrombosis and Vascular Biology 26: 1594-1600, 2006. PMID: 16675721

Motz JT, Fitzmaurice M, Miller A, Gandhi SG, Haka AS, Galindo LH, Dasari RR, Kramer JR, and Feld MS: In vivo Raman spectral pathology of human atherosclerosis and vulnerable plaques. J Biomed Optics 11(2) 021003 (1-8), 2006. PMID: 16674178

Haka AS, Volynskaya Z, Nazemi J, Woletz J, Hicks D, Crowe J, Fitzmaurice M, Dasari RR, and Feld MS: In vivo margin assessment during partial mastectomy breast surgery using Raman spectroscopy. Cancer Research 66: 3317-3322, 2006. PMID: 16540686

Haka AS, Shafer-Peltier KE, Fitzmaurice M, Crowe J, Dasari RR and Feld MS: Detecting breast cancer using Raman spectroscopy. PNAS 102(35):112371-12376, 2005. PMID: 16116095

Breen MS, Lazebnik RS, Fitzmaurice M, Lewin JS, and Wilson DL: Radiofrequency thermal ablation: correlation of hyperacute MR lesion images with tissue response. J Magn Reson Imaging 20(3):475-486, 2004. PMID: 15332256

Lazebnik RS, Breen MS, Fitzmaurice M, Lewin JS, and Wilson DL: Radiofrequency Induced Thermal Lesions: Sub-acute MR appearance and histological correlation. J Magn Reson Imaging 8(4):487-495, 2003. PMID: 14508786

Shafer-Peltier KE, Haka AS, Motz JT, Fitzmaurice M, Dasari RR, Feld MS: Model-based biological Raman spectral imaging. J Cell Biochem 87(S39): S125-S137, 2002. PMID: 12552612

Haka AS, Shafer KE, Fitzmaurice M, Dasari RR, Feld MS: Identifying microcalcifications in benign and malignant breast lesions by probing differences in their chemical composition using Raman spectroscopy. Cancer Research 62(18): 5375-5380, 2002. PMID: 12235010

Shafer-Peltier KE, Haka AS, Fitzmaurice M, Crowe J, Myles J, Dasari RR, and Feld MS: Raman microspectroscopic model of human breast tissue: implications for breast cancer diagnosis in vivo. J Raman Spec 33(7): 552-563, 2002.

Buschman HP, Motz JT, Deinum G, Romer TJ, Fitzmaurice M, Kramer JR, van der Laarse A, Bruschke AV and Feld MS: Diagnosis of human coronary atherosclerosis by morphology-based Raman spectroscopy. Cardiovascular Pathology, 10(2): 59-68, 2001. PMID: 11425599

Buschman HP, Deinum G, Motz JT, Fitzmaurice M, Kramer JR, van der Laarse A, Bruschke AV and Feld MS: Raman microspectroscopy of human coronary atherosclerosis: biochemical assessment of cellular and extracellular morphologic structures in situ. Cardiovascular Pathology 10(2):69-82, 2001. PMID: 11425600

Backman V, Wallace MB, Perelman LT, Arendt JT, Gurjar R, Muller MG, Zhang Q, Zonios G, Kline E, McGillicans T, Shapshay S, Valdez T, Badizadegan K, Crawford JM, Fitzmaurice M, Kabani S, Levin HS, Seiler M, Dasari RR, Itzkan I, Van Dam J, and Feld MS: Detection of preinvasive cancer cells. Nature 406(6791):35-36, 2000. PMID: 10894529

Fitzmaurice M: Principles and pitfalls of diagnostic test development: implications for spectroscopic tissue diagnosis. J. Biomedical Optics 5(2):1-12, 2000. PMID: 10938775