In This Article
- Approximately 85% of tuberous sclerosis complex (TSC) patients develop renal lesions—most, but not all, of which are benign
- Metabolomic evaluation of tissue is a promising approach to managing TSC by differentiating malignant from benign renal tumors
- The emerging analytical tool of HRMAS-MRS reveals the dynamic world of the metabolome at the molecular level, with potential to lead to development of non-invasive detection and early diagnosis of cancer
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Tuberous sclerosis complex (TSC) is a relatively common genetic disease characterized by the development of heterogeneous tumors throughout the body. In the majority of cases, TSC affects the kidneys: Approximately 85% of patients present with renal masses at some point during their lifetimes.
Typically, the tumors caused by TSC are benign; occasionally, they are cancerous. And because conventional magnetic resonance imaging (MRI) does not consistently reveal tumor malignancy, clinical decision-making about disease management can be difficult.
Adam S. Feldman, MD, MPH, director of the Combined Harvard Urologic Oncology Fellowship, urologic oncologist at Massachusetts General Hospital Cancer Center and faculty member of The Carol and James Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital, is leading a multidisciplinary urologic research team to change that. By applying advanced metabolomic imaging of renal masses to carefully selected TSC patients in a translational care study, Dr. Feldman and colleagues aim to improve doctors' ability to differentiate between benign and malignant masses.
"In this study, when we see a patient with a questionable lesion in the kidney, we have the option of adding our advanced imaging techniques of the metabolic spectra to expand the evaluation and get more information from the cells," Dr. Feldman explains.
One of these advanced approaches that Mass General investigators are developing involves ongoing refinement of in vivo magnetic resonance spectroscopy (MRS), combined with an emerging ex vivo technology of high-resolution magic angle spinning (HRMAS). By providing an unprecedented level of information about the molecular beginnings of cancer and benign tumors, this approach reveals a biochemical signature in tissue—a biomarker—before tumors begin to form.
New Spins on Imaging
MRS is a noninvasive technique employed to measure biochemical changes in tissues. MRS variants are useful for comparing biochemical status of normal and abnormal tissues. The newer analytic tool, HRMAS, helps refine tissue analysis.
Leo L. Cheng, PhD, is the biophysicist specializing in medical imaging at the Athinoula A. Martinos Center for Biomedical Imaging, and the inventor of and lead researcher on MRS/HRMAS novel applications on kidney tumors in the TSC study. He views the new imaging approaches as key to the development of a faster, cheaper, less traumatic means of detecting and diagnosing cancers.
"These tools enable us to measure spectra of intact tissue specimens and then correlate tissue cellular metabolic changes with pathology," says Dr. Cheng. "We are now working ex vivo on intact samples we analyze outside the body. Our goal is to translate metabolic knowledge obtained ex vivo into a tool capable of in vivo analysis. That will be of great clinical use and help to patients."
Building on Success
Drs. Feldman and Cheng are building on the efficacy of HRMAS/MRS in prostate cancer detection, diagnosis and management by extending the approach to kidney tumors and TSC patients.
In prior work in prostate cancer via ex vivo HRMAS/MRS analysis, the team identified metabolomic differences between cancerous and benign prostate tissue. Importantly, they also detected early, subtle biochemical changes in the tissue surrounding tumors, called metabolomic field changes or the "halo effect" of cancer.
Now, they are investigating these changes for their potential as non-invasive biomarkers for cancer—the earliest signal from a body under assault by cancer that might enable early, aggressive interventions.
The Age of Metabolomics
The dynamic biochemical suite found in all cells, tissues and fluids of the body is called the metabolome. As an emerging field, the medical specialty of metabolomics analyzes cellular energy flows to decipher healthy and pathological states.
The availability of high-performance analytical tools such as HRMAS-MRS is a major driver for this new age of biochemical disease detection. Metabolomic evaluation offers physicians biochemical information about cells that has not previously been available.
The hope is that in the future, HRMAS-MRS-guided metabolomic medicine may significantly improve cancer patients' care and lives. Mass General's pioneering work in prostate and kidney cancers and TSC patients aims to pave the way for such improvement.
"Continued investigation may help translate ex vivo MRS to novel in vivo MRS biomarkers," Dr. Feldman says, "and in this way, improve the discrimination of kidney cancer from normal tissue by means of non-invasive imaging."
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