Potential Of Magnetic Resonance Spectroscopy Research Articles

Diagnostic potential of magnetic resonance spectroscopy in cognitive impairment in the elderly

To explore the potential use of magnetic resonance spectroscopy (MRS) in the diagnosis of pre-dementia cognitive disorders in elderly people. A total of 65 elderly individuals (37 individuals with mild cognitive impairment (MCI) according to NIA-AA criteria, mean age 67.2 years; 28 controls, mean age 65.2 years) underwent MRS (3.0 T) with posterior cingulate cortex as the region of interest. Absolute concentrations of metabolites (tCr, NAA, Glx, mI, Cho, NAA) were calculated based on their signal intensities. Statistical analysis was performed to assess intergroup differences and correlations. Statistically significant differences were observed between the clinical and control groups in the absolute concentrations of metabolites: mI (MCI 4.97±0.13; controls 4.76±0.15; p=0.04) and NAA/mI (MCI 1.61±0.04; controls 1.73±0.04; p=0.04), as well as in the intensities of the choline-containing compounds signal (MCI 0.215±0.015; controls 0.205±0.005; p=0.04) in the posterior cingulate cortex region. No significant correlations between these changes and age were observed, suggesting the predominant role of neurodegeneration in the pathological process under investigation. The findings highlight the promising nature of MRS as a tool to find the neurodegeneration biomarker.

Abstract 2222: Detecting clinically significant prostate cancers: Tissue metabolomics refines multiparametric MRI-ultrasound fusion prostate biopsy

Abstract The advent of prostate specific antigen (PSA) testing led to increased early prostate cancer (PCa) detection and has decreased PCa-related death. However, PSA is not cancer-specific, and the challenge persists of differentiating those PCa patients with indolent tumors from those requiring definitive therapy. Metabolomic profiles have the potential to capture molecular dynamics of disease and to reflect disease status before cellular manifestations become observable by histopathology. With clinical, multiparametric magnetic resonance imaging (mpMRI)-positive, fusion biopsy-targeted tissue cores and mpMRI-negative controls in a training-testing cohort design, we studied the potential of magnetic resonance spectroscopy (MRS) to yield cancer metabolomic profiles that could help discriminate likely indolent from clinically significant disease. Using MRS-based PCa metabolomic analyses, performed prior to histology, our approach is able to: determine metabolomic relevations identified in fusion biopsy targets, estimate the scale of PCa metabolomic fields, and detect clinically significant disease in tissues deemed benign or low-risk PCa by pathology and imaging. Our intact tissue MRS metabolomics evaluations indicated significant differences in individual prostate tissue metabolites based on Target-Contralateral (Contral) paired comparisons for both Training and Testing cohorts. We identified metabolomic differences among Target prostate biopsy cores obtained from mpMRI lesions of different PI-RADS scores, and between Target and non-target Contral cores. As a retrospective study, we also analyzed data collected at the time of the initial prostate biopsy alongside patient status across follow up. By introducing metabolomics, as compared with using PSAd or PI-RADS alone, the sensitivity predictions increased by 80.0% and 25.0%, respectively; NPV increased by 18.1% and 8.0%; and accuracy for PSAd increased by 13.0%. PI-RADS accuracy stayed the same Our results show that tissue metabolomic profiles could augment current MR-based imaging findings and histopathological evaluations of fusion biopsies for certain patient populations by more accurately characterizing them into clinically significant or insignificant subgroups. In our analyses, tissue metabolomics alone, or its combination with other clinical parameters, improved sensitivity and negative predictive values, as well as overall accuracy, for our testing cohort. This method, which relies on performing tissue MRS of needle biopsy cores prior to histopathologic analysis, causes no interruption to patient care. Findings from our study demonstrate the utility and translational potential of cancer metabolomics in personalized treatment for PCa and encourages the development of in vivo PCa metabolomic imaging to enhance the diagnostic utility of mpMRI. Citation Format: Leo L. Cheng, Adam S. Feldman, Lindsey A. Vandergrift, Isabella H. Muti, Florian Rumpf, Andrew Gusev, Yannick Berker, Marcella R. Cardoso, Taylor L. Fuss, Emily D. Negroponte, Shulin Wu, Felix Ehret, Christopher A. Dietz, Sarah S. Dinges, Thitinan Chulroek, Edouard Nicaise, Piet Habbel, Martin Ayree, Johannes Nowak, Douglas M. Dahl, Chin-Lee Wu, Mukesh Harisinghani. Detecting clinically significant prostate cancers: Tissue metabolomics refines multiparametric MRI-ultrasound fusion prostate biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2222.

Espetroscopia (1H) por ressonância magnética do disco intervertebral lombar no adulto e sua aplicação na rotina imagiológica

Aims – To assess the potential of magnetic resonance spectroscopy (1H‑MRS) in the diagnostic of degenerative disease of the lumbar disc and to advocate the adding of this technique in the classification of the invertebral disc involution vs degeneration (L4‑L5 and L5‑S1) in the clinical routine of lumbar pain status, not related with mechanic causes. Material and method – We studied 102 out of 123 lumbar intervertebral discs. The distribution among spaces was 61 discs at L4‑L5, 41 at L5‑S1 level and 34 at D12‑L1 level. The magnetic resonance studies were performed using a 1.5 T scan-ner. A single‑voxel Point Resolved Spectra Selection (PRESS) technique was used. The ratios [Lac/Nacetyl], [Nacetyl/(Lac+Lip)] and additionally the resonance of lipids were applied to evaluate the biochemistry of the discs, its involution, disc disruption and eventual susceptibility to initiate degeneration process. The ratios and the lipidic value of L4‑L5‑S1 discs were ascertained with the different behavior of D12‑L1. Furthermore, the comparison between L4‑L5, L5‑S1 and D12‑L1 discs was performed according with rating in T2 weighted (adjusted scale 1‑4 from Pfirrmann1 criteria). Results – Related to D12‑L1, the ratios and the lipids of L4‑L5‑S1 discs are statistically different. When used as a complementary of conventional T2 weighted, they have a good discrimination in the all degrees of disc involution vs degeneration. The ratio [Lac/Nacetyl] at L4‑L5‑S1 level was increased when compared to D12‑L1 (p=0.033 for disks with [1+2] score of involution and p=0.004 for disks with score [3+4]). These results suggest that disc degeneration vs involution in higher degrees defines a decrease in the lactate’s peak. The ratio [Nacetyl/(Lac+Lip)] provides a good discrimination of involution between scores [1+2] and [3+4] at L4‑L5 level, presenting the values of the ratios (mean 0.65 and 0.5 with p=0.04). The mean ratio of [Nacetyl/(Lac+Lip)] in the L4‑L5 disc was 1.8 times higher than that of L1‑D12. The lipid spectrum at L4‑L5‑S1 in the higher scores showed no constant prevalence in the resonance frequencies. Conclusion – The (1H) spectroscopy of intervertebral discs may contribute with a supplementary semiology to the conventional MRI. The resonances of L4‑L5 and L5‑S1 discs, involuted or degenerated, must be related with D12‑L1, which are more stable and have lower likelihood of disc degeneration.

Resolution enhancement as a key step towards clinical implementation of Padé-optimized magnetic resonance spectroscopy for diagnostic oncology

Our overall aim is for the full potential of magnetic resonance spectroscopy (MRS) and magnetic resonance spectroscopic imaging (MRSI) to be realized in oncology. This requires mathematics, without which encoded MRS data are entirely uninterpretable. Mathematics based on the conventional approach, the fast Fourier transform (FFT), and ambiguous fittings of Fourier spectra cannot fulfill the rigorous demands of oncology. It is vital to go beyond the FFT and fitting, to obtain reliable quantitative information via MRS about the metabolic content of tissue. None of the available MRS fitting algorithms could provide the clinically needed information with certainty, namely, the metabolite concentrations. Our more advanced method, the fast Pade transform (FPT) is firmly established as a stable, high-resolution processor, with which metabolite concentrations are unequivocally generated for in vitro MRS data associated with prostate, breast and ovarian cancer. Validation of the FPT has also been performed for in vivo MRS of normal human brain from clinical magnetic resonance scanners (1.5 T) as well as from 4 to 7 T scanners. The FPT successfully handles major problems hindering more widespread clinical application of MRS and MRSI, such as separation of noise from signal, resolution of very dense spectra with multiplet resonances (prostate) and overlapping metabolite resonances (breast, brain). In the present paper, we focus upon the implications of resolution enhancement by the FPT. We conclude that the manner by which the FPT achieves its high resolution accuracy dictates a major reformulation of the concept of data acquisition by encoding a small number of short transient time signals to secure good signal-noise ratio. Pade-guided MRS has distinct clinical advantages in combining improved diagnostic accuracy of MRS with shorter examination times. This shortens turn-around time for patients, making MRS efficient and cost-effective. With Pade-based quantification plus FPT-guided encoding of MRS and MRSI data, MRS can become a reliable, cost-effective tool for diagnostics and various aspects of patient care within oncology.

Potential of Magnetic Resonance Spectroscopy in Assessing the Effect of Fatty Acids on Inflammatory Bowel Disease in an Animal Model

People with inflammatory bowel disease (IBD) are at risk for developing colorectal cancer, and this risk increases at a rate of 1% per year after 8-10 years of having the disease. Saturated and omega-6 polyunsaturated fatty acids (PUFAs) have been implicated in its causation. Conversely, omega-3 PUFAs may have the potential to confer therapeutic benefit. Since proton magnetic resonance spectroscopy ((1)H MRS) combined with pattern recognition methods could be a valuable adjunct to histology, the objective of this study was to analyze the potential of (1)H MRS in assessing the effect of dietary fatty acids on colonic inflammation. Forty male Sprague-Dawley rats were administered one of the following dietary regimens for 2 weeks: low-fat corn oil (omega-6), high-fat corn oil (omega-6), high-fat flaxseed oil (omega-3) or high-fat beef tallow (saturated fatty acids). Half of the animals were fed 2% carrageenan to induce colonic inflammation similar to IBD. (1)H MRS and histology were performed on ex vivo colonic samples, and the (1)H MR spectra were analyzed using a statistical classification strategy (SCS). The histological and/or MRS studies revealed that different dietary fatty acids modulate colonic inflammation differently, with high-fat corn oil being the most inflammatory and high-fat flaxseed oil the least inflammatory. (1)H MRS is capable of identifying the biochemical changes in the colonic tissue as a result of inflammation, and when combined with SCS, this technique accurately differentiated the inflamed colonic mucosa based on the severity of the inflammation. This indicates that MRS could serve as a valuable adjunct to histology in accurately assessing colonic inflammation. Our data also suggest that both the type and the amount of fatty acids in the diet are critical in modulating IBD.

Potential of magnetic resonance spectroscopy to detect metastasis in axillary lymph nodes in breast cancer

Focused pathological evaluation of axillary lymph nodes in breast cancer is gaining importance. Nuclear magnetic resonance (NMR) spectroscopy that assesses the whole of the specimen has the potential in evaluating micrometastases. The biochemical changes associated with breast cancer metastases in axillary nodes by in vitro NMR and its use in the detection of axillary metastases in a clinical setting in comparison with conventional histopathology is presented in this study. Eighty-eight lymph nodes obtained from 30 patients with breast cancer were investigated. Histopathology revealed metastases in 20 nodes from 11 patients, while in vitro NMR spectroscopy revealed metastases in 22 nodes. Out of these 22 nodes, 16 were the same, which showed metastases on histopathology, while 6 nodes have shown metastases only on in vitro magnetic resonance spectroscopy (MRS). These 6 nodes with suspicion of metastases on MRS were subjected to reevaluation with serial sectioning and immunohistochemistry, but no additional metastases were revealed. Forty metabolites could be identified from the MR spectrum of lymph nodes. The levels of the glycerophosphocholine-phosphocholine (GPC-PC), choline, lactate, alanine and uridine diphosphoglucose were elevated significantly in nodes with metastases. In addition, the intensity ratio of GPC-PC/threonine (Thr) was higher in nodes with metastases, and using this as marker, MRS detected the axillary metastases with a sensitivity, specificity and accuracy of 80%, 91% and 88%, respectively. Neoadjuvant chemotherapy (NACT) lowered the concentrations of GPC-PC and GPC-PC/Thr ratio. The accuracy of MRS in detecting metastases was 75% in patients who received NACT (n=9) as compared to 96% in those who did not (n=21). Our results demonstrate the potential of in vitro MRS in characterizing the metabolite profile of the axillary nodes with breast cancer metastases. It detected axillary metastases with reasonable accuracy and can be complementary to histopathological evaluation and immunohistochemistry.

Biochemical mechanisms of cyclosporine neurotoxicity.

Proper management of chemotoxicity in transplant patients requires detailed knowledge of the biochemical mechanisms underlying immunosuppressant toxicity. Neurotoxicity is one of the most significant clinical side effects of the immunosuppressive undecapeptide cyclosporine, occurring at some degree in up to 60% of transplant patients. The clinical symptoms of cyclosporine-mediated neurotoxicity consist of decreased responsiveness, hallucinations, delusions, seizures, cortical blindness, and stroke-like episodes that mimic those clinical symptoms of mitochondrial encephalopathy. Clinical computed tomography (CT) and magnetic resonance imaging (MRI) studies have revealed a correlation between clinical symptoms of cyclosporine-mediated neurotoxicity and morphological changes in the brain, such as hypodensity of white matter, cerebral edema, metabolic encephalopathy, and hypoxic damages. Paradoxically, in animal models cyclosporine protects the brain from ischemia-reperfusion (I/R) injury. Interestingly, cyclosporine appears to mediate both neurotoxicity (under normoxic conditions) and I/R protection across the same range of drug concentration. Both toxicity and protection might arise from the intersection of cyclosporine with mitochondrial energy metabolism. This review addresses basic biochemical mechanisms of: 1) cyclosporine toxicity in normoxic brain, and 2) its protective effects in the same organ during I/R. The marked and unparallel potential of magnetic resonance spectroscopy (MRS) as a novel quantitative approach to evaluate metabolic drug toxicity is described.

The Need for Quantitative Biomedical Spectroscopic Imaging through Magnetic Resonance in Oncology beyond the Conventional Fourier-Based Signal Processing

Magnetic Resonance Spectroscopy (MRS) and Magnetic Resonance Spectroscopic Imaging (MRSI) represent a highly promising diagnostic modality for oncology, especially for screening and early detection, by identifying key changes in the emergence and progression of cancer on the molecular level. The combination of anatomic localisation and quantification by metabolite spectra is often decisive in accurate, timely tumour identification. In fact, the potential of MRS and MRSI in oncology has yet to be realized. We argue that in order to achieve this goal, it is necessary go beyond technical (hardware) improvements, important as these are. In this review we demonstrate that many of the limitations of current applications of MRS and MRSI are due to the exclusive reliance upon the conventional mode of data analysis. We then show how these problems can be circumvented by applying recent mathematical advances in signal processing, and, most importantly, how this could impact upon key clinical problems for diagnostics in oncology.

Cerebrospinal fluid lactate and glutamine are reduced in multiple sclerosis

To analyse various metabolites in human cerebrospinal fluid from healthy controls and patients with multiple sclerosis. Cerebrospinal fluid was obtained from patients by lumbar puncture, frozen, redissolved, and analysed for metabolites by proton nuclear magnetic resonance spectroscopy. Significantly lower values for lactate and glutamine were found in patients with multiple sclerosis in comparison with controls. No significant differences were found between patients with the relapsing-remitting and chronic progressive forms of the disease for any of the metabolites measured. There is a concomitant reduction in both lactate and glutamine in the cerebrospinal fluid of patients with multiple sclerosis compared to controls. This may be related to altered astrocytic metabolism during the disease. The results clearly show the diagnostic potential of magnetic resonance spectroscopy in diseases such as multiple sclerosis.

Hydrogen-1, sodium-23, and carbon-13 MR spectroscopy of cartilage degradation in vitro.

Viable bovine nasal cartilage was examined with magnetic resonance (MR) spectroscopy. Digestion of the proteoglycan matrix by papain or trypsin was accompanied by substantial changes in carbon-13, sodium-23, and hydrogen-1 MR spectra and relaxation parameters, with C-13 MR spectra showing the most pronounced changes. These results indicate the potential of MR spectroscopy (and imaging) for noninvasive evaluation of cartilage disease and monitoring of patients with degenerative joint diseases.

Functional pools of oxidative and glycolytic fibers in human muscle observed by 31P magnetic resonance spectroscopy during exercise.

Quantitative probing of heterogeneous regions in muscle is feasible with phosphorus-31 magnetic resonance spectroscopy because of the differentiation of metabolic patterns of glycolytic and oxidative fibers. A differential recruitment of oxidative and glycolytic fibers during exercise was demonstrated in 4 of 10 untrained young men by following changes in phosphate metabolites. Concentrations of inorganic phosphate (Pi), phosphocreatine, and ATP were estimated in the wrist flexor muscles of the forearm at rest, during two cycles of three grades of exercise, and in recovery. At high work levels (40% of maximum strength), two distinct Pi peaks were observed and identified with Pi pools at pH 6.9 and pH 5.9-6.4, respectively. These could be accounted for as follows. At the lowest level of work (using 20% of maximum strength), early recruitment primarily of oxidative (type I) and possibly some intermediate (type IIA) muscle fibers occurs with relatively little net lactate production and consequently little decrease in pH. At higher work loads, however, primarily glycolytic (type IIB) muscle fibers are recruited, which have relatively high net lactate production and therefore generate a second pool of Pi at low pH. ATP depletion (35-54%) and Pi losses accompanied the reduction in ability to perform during the first exercise cycle. When the cycle of graded exercise was repeated immediately, the total Pi remained high but gave rise to only one peak at pH 6.8-7.0. These observations indicated exhaustion of glycolytic type IIB fibers, removal of lactate by high local blood flow, and sustained contractions largely by oxidative type I and IIA fibers. A functional differentiation of fiber types could also be demonstrated during recovery if exercise was stopped while two pools of Pi were still apparent. In the first 3 min of recovery, the Pi peak at pH 6.8-6.9 disappeared almost entirely, whereas the Pi peak at pH 6.0 remained unaltered, reflecting the faster recovery of oxidative type I fibers. The potential of magnetic resonance spectroscopy to characterize oxidative and glycolytic fibers, predict capacity for aerobic performance, and signal the presence of muscle pathology is discussed.

Clinical Potential of Magnetic Resonance Spectroscopy in Renal Disease

Magnetic resonance spectroscopy (MRS), especially of31phosphorus, seeks to collect biochemical and metabolic information related to energy metabolism, intracellular pH, and oxygen delivery to the kidney (1,2). Earlier applications in clinical medicine have been established in diagnosis of metabolic myopathy (3,4), infantile cerebral anoxia (5), stroke (6,7), and in vascular insufficiency of the lower limb (8).