Background: Current clinical management of clear cell renal cell carcinoma (ccRCC) frequently requires surgical excision. Surgery for suspected ccRCC is routinely carried out before histopathological diagnosis, yet up to 20% of enhancing small renal masses are benign and could be managed conservatively. Differences in tissue chemistry, using magnetic resonance spectroscopy of human renal neoplasia biopsies, showed a clear distinction between ccRCC, non-ccRCC and healthy kidney tissue. We aimed to develop a preoperative in vivo diagnosis of renal lesions that could better inform the need for surgery or monitoring. Methods: Using a 3T Prisma magnetic resonance imaging (MRI) scanner we developed an in vivo protocol for measuring chemical changes occurring when a healthy kidney develops a ccRCC lesion. The protocol uses one dimensional respiratory triggered proton point resolved spectroscopy (PRESS), a minimum voxel size of 2 cm3, a shim value of less than 30 Hz and a minimum of 100 averages. Results: Healthy kidneys were compared with three ccRCC lesions, each with a different grade and size. The chemical differences included increases in the resonance intensity for lipid methylene and methyl, choline and creatine. Conclusions: These MRI data now need to be substantiated with a larger study to characterize the malignant potential and relationship to grade and loss of cellular differentiation in ccRCC lesions in vivo.

There is a requirement for an objective method to determine a safe level of low-level military occupational blast, having recognised it can lead to neurological damage. The purpose of the current study was to evaluate the effect of artillery firing training on the neurochemistry of frontline soldiers using two-dimensional (2D) COrrelated SpectroscopY (2D COSY) in a 3-T clinical MR scanner. Ten men considered to be of sound health were evaluated before and after a week-long live firing exercise in two ways. Prior to the live fire exercise, all participants were screened by a clinical psychologist using a combination of clinical interviews and psychometric tests, and were then scanned with 3-T MRI. The protocols included T1- and T2-weighted images for diagnostic reporting and anatomical localisation and 2D COSY to record any neurochemical effects from the firing. No changes to the structural MRI were recorded. Nine substantive and statistically significant changes in the neurochemistry were recorded as a consequence of firing training. Glutamine and glutamate, glutathione, and two of the seven fucose-α (1-2)-glycans were significantly increased. N-acetyl aspartate, myo-inositol + creatine, and glycerol were also increased. Significant decreases were recorded for the glutathione cysteine moiety and tentatively assigned glycan with a 1-6 linkage (F2: 4.00, F1: 1.31 ppm). These molecules are part of three neurochemical pathways at the terminus of the neurons providing evidence of early markers of disruption to neurotransmission. Using this technology, the extent of deregulation can now be monitored for each frontline defender on a personalised basis. The capacity to monitor early a disruption in neurotransmitters, using the 2D COSY protocol, can observe the effect of firing and may be used to prevent or limit these events.

Response to pain therapy is currently by patient self-report. We demonstrate that by evaluating the neurochemistry of a patient, using two-dimensional Correlated SpectroscopY (2D COSY) in a 3T MRI scanner, response to therapy can be recorded. A chronic temporomandibular joint (TMJ) pain patient was evaluated by a pain physician specializing in temporomandibular disorders (TMD), and by 2D COSY, before, and 6 days after treatment with Botulinum Toxin A. Prior to treatment the self-reported pain score was 8/10 and reduced to 0/10 within 24 h of treatment. The neurochemistry of the patient prior to treatment was typical of chronic pain. In particular, the Fuc-α(1-2) glycans were affected. Following treatment, the substrates, α-L Fucose, were elevated and the Fuc-α(1-2) glycans repopulated. The depletion of the molecule assigned the glutathione cysteine moiety, with chronic pain, is indicative of a Glutathione redox imbalance linked to neurodegeneration. This new approach to monitor pain could help discriminate the relative contributions in the complex interplay of the sensory and affective (emotional suffering) components of pain leading to appropriate individualized pharmaceutical drug regimens.

Background: A proposed mechanism of chronic pain is dysregulation between the main inhibitory (GABA) and excitatory (glutamate) neurometabolites of the central nervous system. The level of these neurometabolites appears to differ in individual studies of people with pain compared to pain-free controls across different pain conditions. However, this has yet to be systematically investigated. Aims: To establish whether GABA, glutamate, glutamine and Glx levels differ across pain conditions when compared to pain-free controls. Methods: Five databases were searched. Studies were included if they investigated: 1) A pain condition compared to control. 2) Reported GABA, glutamate, glutamine or glutamate/glutamine level. 3) Used 1H-Magnetic Resonance Spectroscopy (Prospero Project ID CRD42018092170). Data extracted included neurometabolite level, pain diagnosis, and spectroscopy parameters. Meta-analyses were conducted to establish the difference in neurometabolite level between participants with pain and pain-free controls for different pain conditions. The MRS-Q was developed from existing clinical consensus to allow for the assessment of quality in the included studies. Results: Thirty-five studies were included investigating combinations of migraine (n = 11), musculoskeletal pain (n = 8), chronic pain syndromes (n = 9) and miscellaneous pain (n = 10). Higher GABA levels were found in participants with migraine compared to controls (Hedge's G 0.499, 95%CI: 0.2 to 0.798). In contrast, GABA levels in musculoskeletal pain conditions (Hedge's G -0.189, 95%CI: 0.530 to 0.153) and chronic pain syndromes (Hedge's G 0.077, 95%CI: 1.612 to 1.459) did not differ from controls. Results for other brain neurometabolites revealed significantly higher levels for glutamate in participants with migraine and Glx in chronic pain syndromes compared to controls. Conclusion: These results support the theory that underlying neurometabolite levels may be unique in different pain conditions and therefore representative of biomarkers for specific pain conditions.