Dr. Spernyak has been involved in a broad range of research projects incorporating the use of magnetic resonance imaging (MRI) for studying small animal model of disease. His recent interests have focused primarily in three areas, a) development and assessment of novel MRI/PDT contrast agents for the purpose of combining imaging and therapy within a single compound, b) use of MRI to non-invasively characterize changes in tumor microvasculature arising from anti-cancer therapies, and c) application of balanced, steady-state free precession imaging for efficient and accurate measurement of tissue MR relaxation rates.
Collaborating with Dr. Ravindra Pandey (Cell Stress Biology), our lab has been developing and characterizing novel, multi-functional imaging agents for use in both imaging and photodynamic therapy (PDT). Combining imaging capabilities with a tumor-specific therapeutic has multiple advantages, including improved tumor boundary delineation and non-invasive tracking of tumor uptake and pharmacokinetics. These capabilities may lead to improved prognostic indicators on the efficacy of PDT treatment based upon imaging biomarkers.
Dynamic-contrast enhanced MR imaging is being utilized to probe changes in vascular function as a result of chemotherapy (e.g. doxorubicin) or biophysical therapies such as PDT or whole body hyperthermia. The microvasculature architecture within tumors differs from normal vasculature in a number of ways. Tumor vasculature is chaotic and hyper-permeable, often exhibiting reduced blood flow, which in turn can reduce the efficacy of anti-cancer treatments. Using MRI, changes in tumor blood flow and vascular function can be studied in situ, leading to greater understanding of the vascular effects of such treatments and potentially to better outcomes.
Critical to this work is the ability to perform rapid measurement of tissue relaxation rates in vivo with a high degree of accuracy and sensitivity. Balanced, steady-state free precession (bSSFP) imaging is being explored in a preclinical environment as a means of rapid relaxometry, as it offers many advantages over alternative methods, namely a) high signal to noise ratios, b) improved spatial homogeneity over a large volume, c) short acquisition times, and d) simultaneous extraction of both T1 and T2 relaxation rates within a single MRI dataset. This methodology is currently being applied for use in novel contrast agent development, microvascular assessment, and high-resolution in vivo microscopy.
Goswami LN, White WH, Spernyak JA, Ethirajan M, Chen Y, Missert JR, Morgan J, Mazurchuk R, Pandey RK. Synthesis of Tumor-avid Photosensitizer-Gd(III)DTPA conjugates: impact of the number of gadolinium units in T1/T2 relaxivity, intracellular localization, and photosensitizing efficacy. Bioconjugate chemistry 2010; 21(5):816-827
Spernyak JA, Mazurchuk R, Batt C, Missert JR, Turowski S, Chen Y, Goswami L, Patel NJ, Ethirajan M, White WH, Pandey RK. Hexylether derivative of pyropheophorbide-a (HPPH) on conjugating with 3gadolinium(III) aminobenzyldiethylenetriaminepentaacetic acid shows potential for in vivo tumor imaging (MR, Fluorescence) and photodynamic therapy. Bioconjugate chemistry 2010; 21(5):828-835
Chintala S, Vaughan MM, Horowitz JM, Meeder BA, Busch K, Patel S, Torres G, Mazurchuk R, Spernyak JA, Novak EK, Swank RT. The Vps33a gene regulates behavior and cerebellar Purkinje cell number. Brain research 2009;1266:18-28
Paul AK, Lobarinas E, Simmons R, Wack D, Luisi JC, Spernyak J, Mazurchuk R, Abdel-Nabi H, Salvi R. Metabolic imaging of rat brain during pharmacologically-induced tinnitus. NeuroImage 2009; 44(2):312-318
Riddell JR, Bshara W, Moser MT, Spernyak JA, Foster BA, Gollnick SO.Peroxiredoxin 1 controls prostate cancer growth through Toll-like receptor 4-dependent regulation of tumor vasculature. Cancer research 2011;71(5):1637-1646
Sen A, Capitano ML, Spernyak JA, Schueckler JT, Thomas S, Singh AK, Evans SS, Hylander BL, Repasky EA. Mild elevation of body temperature reduces tumor interstitial fluid pressure and hypoxia and enhances efficacy of radiotherapy in murine tumor models. Cancer research 2011; 71(11):3872-3880
Seshadri M, Bellnier DA, Vaughan LA, Spernyak JA, Mazurchuk R, Foster TH, Henderson BW. Light delivery over extended time periods enhances the effectiveness of photodynamic therapy. Clinical cancer research 2008;14(9):2796-2805
Torres G, Hallas BH, Gross KW, Spernyak JA, Horowitz JM. Magnetic resonance imaging and spectroscopy in a mouse model of schizophrenia.Brain research bulletin 2008; 75(5):556-561
Turowski SG, Seshadri M, Loecher M, Podniesinski E, Spernyak JA, Mazurchuk RV. Performance of a novel piezoelectric motor at 4.7 T: applications and initial tests. Magnetic resonance imaging 2008; 26(3):426-432
Jell J, Patel MS, Alhonen L, Deeb KK, Barrero C, Kisiel ND, Diegelman P,Spernyak JA, Mazurchuk R, Hensen ML, Merali S, Porter CW. Genetically altered expression of spermidine/spermine N1-acetyltransferase affects fat metabolism in mice via acetyl-CoA. Journal of biological chemistry 2007;282(11):8404-8413
Pliss L, Mazurchuk R, Spernyak JA, Patel MS. Brain MR imaging and proton MR spectroscopy in female mice with pyruvate dehydrogenase complex deficiency. Neurochemical research 2007; 32(4-5):645-654
Seshadri M, Spernyak JA, Maiery PG, Cheney RT, Mazurchuk R, Bellnier DA.Visualizing the acute effects of vascular-targeted therapy in vivo using intravital microscopy and magnetic resonance imaging: correlation with endothelial apoptosis, cytokine induction, and treatment outcome. Neoplasia (New York, N.Y.) 2007; 9(2):128-135
Dorazio SJ, Tsitovich PB, Siters KE, Spernyak JA, Morrow JR. Iron(II) PARACEST MRI contrast agents. Journal of the American Chemical Society2011; 133(36):14154-14156
Bakin A, Safina A, Spernyak J, Mazurchuck R. TGF-b signaling in tumor angiogenesis and metastasis. Clinical and experimental metastasis 2007;24(4):269-270
Bakin AV, Safina A, Mazurchuck R, Spernyak J. TGF-b1 signaling enhances tumor angiogenesis and metastasis. Proceedings of the American Association for Cancer Research Annual Meeting 2007; 48:987
Seshadri M, Spernyak JA, Mazurchuk R, Vaughan LA, Bellnier DA, Henderson BW. Fluence rate effects on tumor oxygenation during photodynamic therapy for cancer: A BOLD (fMRI) experience. Proceedings of the American Association for Cancer Research Annual Meeting 2007; 48:1292-1293