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Mutations in the ATP1A3 gene (which encodes the main α subunit in neuronal Na+/K+-ATPases) cause various neurological syndromes including alternating hemiplegia of childhood. This rare disorder is characterized by paroxysmal episodes of hemiplegia, dystonia, oculomotor abnormalities, and occasionally developmental regression. Approximately 50% of alternating hemiplegia of childhood patients also have epilepsy, which is either focal or generalized. Seizures are often drug resistant. We report a 10-year-old girl with the D801N ATP1A3 mutation and alternating hemiplegia of childhood who manifested with drug-resistant focal seizures as an infant and throughout childhood. At the age of about10.5 years, her epilepsy evolved into electrical status epilepticus in sleep with generalized discharges. These changes coincided with developmental regression consistent with epileptic encephalopathy. Additionally, MRI and MR spectroscopy showed new cortical atrophy and markedly depressed N-acetyl aspartate peaks compared to previous normal studies. Electrical status epilepticus in sleep resolved after medication adjustments. She, now, only four months after her diagnosis of electrical status epilepticus in sleep, has regained most of the skills that were lost only a few months earlier. Our observations document that alternating hemiplegia of childhood can result in the above-described unique features; particularly, progression of focal epilepsy to electrical status epilepticus in sleep with generalized features and reversible epileptic encephalopathy.

MRI interpretations of the pediatric brain are often challenging for general radiologists and clinicians because MR signals and morphology are continuously changing in the developing brain. Furthermore, the developing brain reacts differently to injuries, resulting in imaging characteristics that differ from those of the mature brain. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method for assessing neurological abnormalities at the microscopic level and measures in vivo brain metabolites using a clinical MR machine. In MR examinations of the pediatric brain, 1H-MRS demonstrates its powerful diagnostic capability when MRI is insufficient for diagnostic features. MRI and 1H-MRS may be complementary tools for diagnosing and monitoring diseases. However, there is currently no consensus on how to include 1H-MRS in clinical MR examinations. An overview of the clinical implementation of 1H-MRS for the assessment of early pediatric developmental brains as well as the diagnosis, prognostification, and disease monitoring of various non-neoplastic brain disorders, including neonatal encephalopathies and neurometabolic/neurodegenerative diseases, was provided herein. Qualitative and quantitative 1H-MRS is a powerful non-invasive tool for accessing various brain metabolites to confirm age appropriate peaks and detect abnormal peaks or deficient or reduced peaks, which may facilitate the identification of metabolic and neurodegenerative disorders as well as damage associated with hypoxic-ischemic encephalopathy (HIE). Moreover, 1H-MRS has potential as a biomarker for monitoring therapeutic efficacy in metabolic diseases and neonatal HIE. It also provides insights into the pathophysiologies of various disorders, which may facilitate the use of novel therapeutic approaches. Therefore, 1H-MRS needs to be included more frequently in routine clinical MR examinations of pediatric patients with neurological disorders.

BACKGROUND: Patients with recurrent glioblastoma (GBM) are often treated with antiangiogenic agents, such as bevacizumab (BEV). Despite therapeutic promise, conventional MRI methods fail to help determine which patients may not benefit from this treatment. PURPOSE: To use MR spectroscopic imaging (MRSI) with intermediate and short echo time to measure corrected myo-inositol (mI)normalized by contralateral creatine (hereafter, mI/c-Cr) in participants with recurrent GBM treated with BEV and to investigate whether such measurements can help predict survivorship before BEV initiation (baseline) and at 1 day, 4 weeks, and 8 weeks thereafter. MATERIALS AND METHODS: In this prospective longitudinal study (2016–2020), spectroscopic data on mI—a glial marker and osmoregulator within the brain—normalized by contralateral creatine in the intratumoral, contralateral, and peritumoral volumes of patients with recurrent GBM were evaluated. Area under the receiver operating characteristic curve (AUC) was calculated for all volumes at baseline and 1 day, 4 weeks, and 8 weeks after treatment to determine the ability of mI/c-Cr to help predict survivorship. RESULTS: Twenty-one participants (median age ± standard deviation, 62 years ± 12; 15 men) were evaluated. Lower mI/c-Cr in the tumor before and during BEV treatment was predictive of poor survivorship, with receiver operating characteristic analyses showing an AUC of 0.75 at baseline, 0.87 at 1 day after treatment, and 1 at 8 weeks after. A similar result was observed in contralateral normal-appearing tissue and the peritumoral volume, with shorter-term survivors having lower levels of mI/c-Cr. In the contralateral volume, a lower ratio of mI to creatine (hereafter, mI/Cr) predicted shorter-term survival at baseline and all other time points. Within the peritumoral volume, lower mI/c-Cr levels were predictive of shorter-term survival at baseline (AUC, 0.80), at 1 day after treatment (AUC, 0.93), and at 4 weeks after treatment (AUC, 0.68). CONCLUSION: Lower levels of myo-inositol normalized by contralateral creatine within intratumoral, contralateral, and peritumoral volumes were predictive of poor survivorship and antiangiogenic treatment failure as early as before bevacizumab treatment. Adapting MR spectroscopic imaging alongside conventional MRI modalities conveys critical information regarding the biologic characteristics of tumors to help better treat individuals with recurrent glioblastoma. Clinical trial registration no. NCT02843230 © RSNA, 2021 Online supplemental material is available for this article.

The underlying mechanisms of many pain conditions are not known and many conditions have no effective treatment. Modern dynamic neuroimaging have increased the understanding of altered CNS processing in different pain conditions. This chapter describes the use of advanced MR imaging techniques like fMRI, MR spectroscopy, and diffusion-weighted imaging as well as more established techniques like PET and SPECT in pain conditions in general with more focused attention to fibromyalgia.

Background Giant tumefactive perivascular spaces (PVSs) are uncommon benign cystic lesions. They can imitate cystic neoplasms. Purpose To evaluate the contribution of advanced neuro magnetic resonance imaging (MRI) techniques in the diagnosis of giant tumefactive PVSs and to further characterize these unusual cerebral lesions. Material and Methods The MRI scans of patients with tumefactive PVS diagnosed between 2010 and 2019 were retrospectively reviewed. All imaging studies included three plane conventional cerebral MRI sequences as well as precontrast 3D T1 MPRAGE, post-gadolinium 3D T1 acquisitions, sagittal plane 3D T2 SPACE, diffusion-weighted imaging, and time-of-flight (TOF) angiography. Some patients received perfusion MR, MR spectroscopy, diffusion tensor imaging (DTI), and contrast-enhanced TOF MR angiography. Results A perforating vessel was demonstrated in 16 patients (66.7%) by TOF imaging. In four patients, there were intracystic vascular collaterals on contrast-enhanced TOF MR angiography. Septal blooming was observed in four patients in susceptibility-weighted imaging. On perfusion MR, central hyperperfusion was observed in four patients, and peripheral hyperperfusion was observed in one patient. On MR spectroscopy, choline increase was observed in two patients, and there was a lactate peak in three patients, and both a choline increase and lactate peak in one patient. On DTI, there was fiber distortion in five patients and fiber deformation in one patient. Conclusion Advanced MRI techniques and 3D volumetric high-resolution MRI sequences can provide a valuable contribution to the diagnosis and can be successfully used in the management of these lesions.

Purpose The goal of this study was to combine a specialized acquisition method with a new quantification pipeline to accurately and efficiently probe the metabolism of hyperpolarized 13 C-labeled compounds in vivo. In this study, we tested our approach on [2-13 C]pyruvate and [1-13 C]α-ketoglutarate data in rat orthotopic brain tumor models at 3T. Methods We used a multiband metabolite-specific radiofrequency (RF) excitation in combination with a variable flip angle scheme to minimize substrate polarization loss and measure fast metabolic processes. We then applied spectral-temporal denoising using singular value decomposition to enhance spectral quality. This was combined with LCModel-based automatic 13 C spectral fitting and flip angle correction to separate overlapping signals and rapidly quantify the different metabolites. Results Denoising improved the metabolite signal-to-noise ratio (SNR) by approximately 5. It also improved the accuracy of metabolite quantification as evidenced by a significant reduction of the Cramer Rao lower bounds. Furthermore, the use of the automated and user-independent LCModel-based quantification approach could be performed rapidly, with the kinetic quantification of eight metabolite peaks in a 12-spectrum array achieved in less than 1 minute. Conclusion The specialized acquisition method combined with denoising and a new quantification pipeline using LCModel for the first time for hyperpolarized 13 C data enhanced our ability to monitor the metabolism of [2-13 C]pyruvate and [1-13 C]α-ketoglutarate in rat orthotopic brain tumor models in vivo. This approach could be broadly applicable to other hyperpolarized agents both preclinically and in the clinical setting.

We here report on a 60-year-old woman with familial Mediterranean fever (FMF) who developed cognitive impairment 16 years after initial diagnosis. On MRI, a new extensive white matter lesion in the right frontal lobe with mild local mass effect but without contrast enhancement was detectable and classified as a tumefactive lesion. Additional MR spectroscopy showed markedly increased choline levels accompanied by a significant lactate peak, highly suggestive of a low-florid demyelinating process. Although diffuse central nervous system (CNS) lesions have been described in single FMF cases, tumefactive lesions have not been observed in FMF patients without concomitant multiple sclerosis. In summary, this case highlights rare differential diagnoses of atypical, inflammatory CNS lesions and the clinical utility of MR spectroscopy.Die Autoren berichten in dem vorgestellten Fall von einer 60-jährigen Frau mit vorbekanntem familiärem Mittelmeerfieber (FMF), die 16 Jahre nach Diagnosestellung subakut kognitive Defizite entwickelt hatte. In der Bildgebung mittels Magnetresonanztomographie (MRT) zeigte sich als mögliche Erklärung dafür eine neue, frontal rechts gelegene Läsion mit leichtem Masseneffekt, aber ohne Kontrastmittelaufnahme, die als tumefaktive Läsion eingestuft wurde. Eine ergänzende MR-Spektroskopie zeigte einen deutlich erhöhten Cholin-Peak zusammen mit einem Laktat-Peak, was einen niedrigfloriden demyelinisierenden Prozess nahelegte. Auch wenn diffuse Läsionen des zentralen Nervensystems (ZNS) bei FMF vorbekannt sind, so wurden bislang tumefaktive Läsionen bei FMF ohne begleitende Multiple Sklerose nicht beschrieben. Zusammenfassend werden anhand dieses Falls seltene Differenzialdiagnosen von atypischen ZNS-Läsionen und der klinische Nutzen der MR-Spektroskopie hervorgehoben.

Stereotactic radiosurgery (SRS) is a treatment option in the initial management of patients with brain metastases. While its efficacy has been demonstrated in several prior studies, treatment-related complications, particularly symptomatic radiation necrosis (RN), remains as an obstacle for wider implementation of this treatment modality. We thus examined risk factors associated with the development of symptomatic RN in patients treated with SRS for brain metastases.We performed a retrospective review of our institutional database to identify patients with brain metastases treated with SRS. Diagnosis of symptomatic RN was determined by appearance on serial MRIs, MR spectroscopy, requirement of therapy, and the development of new neurological complaints without evidence of disease progression.We identified 323 brain metastases treated with SRS in 170 patients from 2009 to 2018. Thirteen patients (4%) experienced symptomatic RN after treatment of 23 (7%) lesions. After SRS, the median time to symptomatic RN was 8.3 months. Patients with symptomatic RN had a larger mean target volume (p0.0001), and thus larger V100% (p0.0001), V50% (p0.0001), V12Gy (p0.0001), and V10Gy (p=0.0002), compared to the rest of the cohort. Single-fraction treatment (p=0.0025) and diabetes (p=0.019) were also significantly associated with symptomatic RN.SRS is an effective treatment option for patients with brain metastases; however, a subset of patients may develop symptomatic RN. We found that patients with larger tumor size, larger plan V100%, V50%, V12Gy, or V10Gy, who received single-fraction SRS, or who had diabetes were all at higher risk of symptomatic RN.

PURPOSE This study is to investigate time-resolved 13 C MR spectroscopy (MRS) as an alternative to imaging for assessing pyruvate metabolism using hyperpolarized (HP) [1-13 C]pyruvate in the human brain. METHODS Time-resolved 13 C spectra were acquired from four axial brain slices of healthy human participants (n = 4) after a bolus injection of HP [1-13 C]pyruvate. 13 C MRS with low flip-angle excitations and a multichannel 13 C/1 H dual-frequency radiofrequency (RF) coil were exploited for reliable and unperturbed assessment of HP pyruvate metabolism. Slice-wise areas under the curve (AUCs) of 13 C-metabolites were measured and kinetic analysis was performed to estimate the production rates of lactate and HCO3- . Linear regression analysis between brain volumes and HP signals was performed. Region-focused pyruvate metabolism was estimated using coil-wise 13 C reconstruction. Reproducibility of HP pyruvate exams was presented by performing two consecutive injections with a 45-minutes interval. RESULTS [1-13 C]Lactate relative to the total 13 C signal (tC) was 0.21-0.24 in all slices. [13 C] HCO3- /tC was 0.065-0.091. Apparent conversion rate constants from pyruvate to lactate and HCO3- were calculated as 0.014-0.018 s-1 and 0.0043-0.0056 s-1 , respectively. Pyruvate/tC and lactate/tC were in moderate linear relationships with fractional gray matter volume within each slice. White matter presented poor linear regression fit with HP signals, and moderate correlations of the fractional cerebrospinal fluid volume with pyruvate/tC and lactate/tC were measured. Measured HP signals were comparable between two consecutive exams with HP [1-13 C]pyruvate. CONCLUSIONS Dynamic MRS in combination with multichannel RF coils is an affordable and reliable alternative to imaging methods in investigating cerebral metabolism using HP [1-13 C]pyruvate.

Altered brain metabolism contributes to pathophysiology in cerebrovascular and neurodegenerative diseases such as stroke and Alzheimer’s disease. Current clinical tools to study brain metabolism rely on positron emission tomography (PET) requiring specific hardware and radiotracers, or magnetic resonance spectroscopy (MRS) involving technical complexity. In this review we highlight deuterium metabolic imaging (DMI) as a novel translational technique for assessment of brain metabolism, with examples from brain tumor and stroke studies. DMI is an MRS-based method that enables detection of deuterated substrates, such as glucose, and their metabolic products, such as lactate, glutamate and glutamine. It provides additional detail of downstream metabolites compared to analogous approaches like fluorodeoxyglucose (FDG)-PET, and can be implemented and executed on clinical and preclinical MR systems. We foresee that DMI, with future improvements in spatial and temporal resolutions, holds promise to become a valuable MR imaging (MRI) method for non-invasive mapping of glucose uptake and its downstream metabolites in healthy and diseased brain.

Phosphorous magnetic resonance spectroscopy (31P-MRS) is suited to noninvasively investigate energy metabolism and to detect molecules containing phosphorus in the human brain. The aim of this long...

Molecular and imaging studies are applied along with histopathology in diagnosis and differential diagnosis of brain gliomas and they enable personalised clinical management. With knowledge of the patient’s clinical condition, a decision whether to observe the patient or proceed to immediate surgical treatment is made based on imaging results. On the other hand, knowledge of molecular predictive markers allows optimisation of chemotherapeutic decisions, e.g., introduction of personalised therapy (application of such drugs as temozolomide, bevacizumab, vemurafenib, dabrafenib and trametinib).

Blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) studies have shown that drug-dependent patients are activated in different addictive brain areas under the stimulation of relevant environmental cues, which in turn leads to craving and relapse. This study uses magnetic resonance spectroscopy to measure brain temperature to explore the brain temperature changes in different addictive brain regions of heroin and methamphetamine addicts in a short-term withdrawal state and to explore whether the quantitative index of brain temperature change can be used as a diagnostic drug Methods. The subjects were scanned by resting-state MRI spectroscopy first and then subjected to MRI spectroscopy scanning under visual stimulation. The subjects were required to watch the heroin/meth-related clue pictures carefully during visual stimulation. The measured chemical shift value of N-acetyl-aspartic acid (NAA) is substituted into the brain temperature calculation formula T = 37 + 100 to obtain the brain temperature before and after visual stimulation. In addition, the anxiety and depression states of heroin and methamphetamine-dependent patients were evaluated. Results. There was no statistically significant change in the brain temperature of the prefrontal cortex before and after visual stimulation in heroin and methamphetamine-dependent subjects; compared with the normal group, there was no change in prefrontal cortex brain temperature before and after visual stimulation in heroin and methamphetamine-dependent subjects. Statistical Significance. The changes of hippocampal temperature before and after visual stimulation in methamphetamine-dependent patients were not statistically significant; compared with the normal group, there was no statistically significant difference in the changes of hippocampal temperature before and after visual stimulation in methamphetamine-dependent patients. Conclusion. This study initially found that the visual cues related to heroin and methamphetamine were not enough to cause significant changes in the brain temperature of the prefrontal cortex.

PURPOSE To investigate the editing-pulse flip angle (FA) dependence of editing efficiency and ultimately to maximize the edited signal of commonly edited MR spectroscopy (MRS) signals, such as gamma-aminobutyric acid (GABA) and lactate. METHODS Density-matrix simulations were performed for a range of spin systems to find the editing-pulse FA for maximal editing efficiency. Simulations were confirmed by phantom experiments and in vivo measurements in 10 healthy participants using a 3T Philips scanner. Four MEGA-PRESS in vivo measurements targeting GABA+ and lactate were performed, comparing the conventional editing-pulse FA (FA = 180°) to the optimal one suggested by simulations (FA = 210°). RESULTS Simulations and phantom experiments show that edited GABA and lactate signals are maximal at FA = 210°. Compared to conventional editing (FA = 180°), in vivo signals from GABA+ and lactate signals increase on average by 8.5% and 9.3%, respectively. CONCLUSION Increasing the FA of editing-pulses in the MEGA-PRESS experiment from 180° to 210° increases the edited signals from GABA+ and lactate by about 9% in vivo.

Background: Intracranial cystic lesions are unnatural cavities in which the continuity of the brain parenchyma is disrupted because of different pathologies such as infections and tumors containing proteinaceous fluid and/or cellu-lar/necrotic materials. Aim of Study: The purpose of this study is to investigate the value of DWI in differentiation of the common intracranial intra-axial cystic/necrotic lesions. Patients and Methods: This is a descriptive study, con-ducted from July 2019 till February 2021. It is included twenty-four adult patients of either sex with a cystic/necrotic intra-axial brain lesion with variable perifocal edema and rim enhancement on post-contrast study at MRI unit, radiology department, Ain Shams University (ASU) Hospital. All exam-inations carried out after signing the informed consent by the patient himself or his guardian if the patient is incapacitated by any means. Results: The inflammatory lesions, the wall ADC values were not uniform. We found the lowest ADC value in contrast enhanced part of the pyogenic abscess 0.922x10-3 mm2/s and the highest ADC wall value 1.529x10-3 mm2/s found in toxoplasmosis abscess. There was a significant difference in the wall ADC values of metastatic lesions mean ADC of contrast enhanced part was 1.32±0.18x10-3 mm2/s and 0.80 ±0.13x10-3 mm2/s found in PCNSL, with a cut off value, sensitivity, specificity, positive predictive value (PPV) negative predictive value (NPV) and p-value of: 1.035, 100%, 100%, 100%, 100% and 0.007 respectively. The mean ADC value of the surrounding edema in our study were measured 1.40 ±0.11x10-3 mm2/s for abscess group and 1.59±0.31x10-3 mm2/s for malignant group with insignificant p-value of 0.201. Conclusion: Further more MR techniques may be used for discrimination brain abscess from cystic or necrotic tumors, as diffusion tensor imaging (DTI), MR spectroscopy and perfusion weighted imaging as well as positron emission tomography computed tomography (PET-CT) may be helpful. The use of these additional techniques will help to improve the accuracy of MR in differentiating brain abscess from cystic or necrotic tumors.

BACKGROUND AND PURPOSE This study aimed to highlight anorexia nervosa-related metabolic changes in different brain regions with different gray and white matter contents. METHODS In a prospective study, 25 anorexic patients with mean body mass index (BMI) of 14.79 kg/m2 (range 10.04-20.58) were compared with 15 healthy controls with mean BMI of 21.08 kg/m2 (range 18.36-27.34). Two-dimensional magnetic resonance spectroscopic imaging was acquired in the axial plane above the corpus callosum, including frontal, precentral, postcentral, cingular, and parietal regions, as well as the precuneus, each voxel containing gray and white matter. RESULTS In the anorexic group, a significant increase of choline/creatine was observed in all brain regions except the precuneus: frontal (p = 0.009), cingulate (p = 0.001), precentral (p = 0.001), postcentral (p = 0.001), and parietal (p = 0.002); and in white and gray matter (p< 0.001). Macromolecules09/creatine was decreased in the following regions: frontal (p = 0.003), cingulate (p< 0.001), precentral (p = 0.004), and precuneus (p = 0.007), and in white and gray matter (p< 0.05). We observed significantly lower values of N-acetyl aspartate/creatine in the frontal (p < 0.001) and precentral (p< 0.001) regions and in voxels containing more than 50% white matter (p = 0.001); and significantly lower values of myo-inositol/creatine in the precentral (p = 0.006), postcentral (p< 0.001), and precuneus (p = 0.006) regions. CONCLUSIONS We observed an increase in choline/creatine in anorexics, possibly reflecting increased cell turnover; a decrease in macromolecules, which was particularly low in the cingulate and precuneus the former being known to be altered in eating disorders; and a decrease in N-acetyl aspartate/creatine considered as a marker of neuronal density and function.

KARS encodes lysyl-tRNA synthetase, which is essential for protein translation. KARS mutations sometimes cause impairment of cytoplasmic and mitochondrial protein synthesis, and sometimes lead to progressive leukodystrophies with mitochondrial signature and psychomotor regression, and follow a rapid regressive course to premature death. There has been no disease-modifying therapy beyond supportive treatment. We present a 5-year-old male patient with an asymmetrical leukodystrophy who showed overt evidence of mitochondrial dysfunction, including elevation of lactate on brain MR spectroscopy and low oxygen consumption rate in fibroblasts. We diagnosed this patient's condition as KARS-related leukodystrophy with cerebral calcification, congenital deafness, and evidence of mitochondrial dysfunction. We employed a ketogenic diet as well as multiple vitamin supplementation with the intention to alleviate mitochondrial dysfunction. The patient showed alleviation of his psychomotor regression and even partial restoration of his abilities within 4 months. This is an early report of a potential disease-modifying therapy for KARS-related progressive leukodystrophy without appreciable adverse effects.

Background: Differentiation of brain lesions by conventional MRI alone is not enough. The introduction of sophisticated imaging methods, such as MR Spectroscopy (MRS), will contribute to accurate differentiation. Objective: To determine the diagnostic accuracy of MRS in differentiating neoplasm and non-neoplastic brain lesion. Methodology: This is a cross-sectional descriptive study conducted at Khartoum State from the period of 2015 to 2017. Thirty cases with brain lesions were included in the study investigated with MRS (Single-voxel spectroscopy) and conventional MRI. A comparison of MRS findings and histopathologic analysis was performed. The ratios of Cho/Cr and Cho/NAA were analyzed and compared between neoplastic and non-neoplastic brain masses. Data were analyzed using SPSS version 23. Results: Out of the 30 patients affected with brain lesions, there were 16 females and 14 males with a mean age of 44 +- 18 years. The ratios of Cho/Cr and Cho/NAA were higher in gliomas, astrocytoma, and meningioma than non-neoplastic lesions. Kappa statistical value (K) showed a good agreement between MRS and histopathological analysis (K= 0.60). The diagnostic accuracy of MRS was 100%, with 82.60% sensitivity, 85.71% specificity, 95% PPV, and 60% NPV. Conclusion: MRS has high diagnostic accuracy in differentiating neoplasm from non-neoplastic brain tumors. The elevation ratios of Choline-to- N-acetyl aspartate and choline-to- creatine can help neurosurgeons and clinicians differentiate benign from malignant masses.

Background and purpose Magnetic resonance (MR) biomarkers are emerging for sports-related traumatic brain injury (TBI), but the effect of play time has not been characterized. Our goal was to characterize brain and inflammatory marker changes as a function of play time. Methods Nine male players (21±2 years old) from a single collegiate basketball team were included. MR imaging (MRI), MR spectroscopy, and plasma were collected pre, mid, and postseason. Game time played was calculated for each subject. Changes in brain volume, diffusion tensor imaging (DTI), metabolites (normalized to total creatine, tCr), temperature, structural and functional connectivity, and inflammatory markers were quantified. Results Myo-inositol/tCr in the left frontal white matter and brain temperature in the left frontal lobe varied significantly between time points. Glutamate (Glu/tCr) in the right frontal white matter and N-acetylaspartate in the posterior cingulate cortex (PCC) were negatively associated with minutes played. Midseason play time was associated with stronger blood-oxygen-level-dependent correlations between PCC and occipital areas, and weaker correlations between PCC and superior frontal connectivity. PCC Glu/tCr was positively associated with connectivity between the PCC and posterior supramarginal gyrus at preseason and with connectivity across time points among several right hemisphere regions. Volume, DTI, and inflammatory markers did not vary significantly. Conclusion Given that MR parameters vary with game play time in the absence of diagnosed injury, play time should be considered as a factor in sports-related TBI research.

Background Clinical and/or neuroimaging changes after whole-brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for metastatic brain tumor(s) present the clinical dilemma of differentiating tumor recurrence from radiation necrosis. Several imaging modalities attempt to answer this clinical question, including magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) computed tomography (CT). We evaluated our experience regarding the ability of MRS and PET CT to differentiate tumor recurrence from radiation necrosis in patients who have received WBRT or SRS. Methods We retrospectively reviewed records of 242 patients with previous WBRT or SRS to identify those who had MRS and/or PET CT to differentiate tumor recurrence from radiation necrosis. Patients were sorted into true-positive, false-positive, false-negative, and true-negative groups on the basis of imaging interpretation and clinical course combined with surgical pathology results or reaction to nonsurgical treatments including SRS, dexamethasone, or observation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were then calculated. Results Of 25 patients presenting such diagnostic questions, 19 were evaluated with MRS and 13 with PET CT. MRS sensitivity was 100%, specificity was 50%, and accuracy was 81.8%, whereas PET CT sensitivity was 36.4%, specificity was 66.7%, and accuracy was 42.9%. Conclusions MRS has better accuracy than PET CT and a high negative predictive value, therefore making it more useful in distinguishing recurrent tumor from radiation necrosis. We encourage correlation with symptoms at imaging to aid in clinical decision making.

Background Alterations in glycolysis are central to the increasing incidence of non-alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non-invasive technologies to understand the development of hepatic metabolic aberrations. Purpose To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life-long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. Study type Prospective. Animal model Twenty-eight male guinea pigs weaned onto a control diet (N = 14) or WD (N = 14). Field strength/sequence 3 T; T1-weighted gradient echo, T2-weighted spin-echo, three-dimensional gradient multi-echo fat-water separation (IDEAL-IQ), and broadband point-resolved spectroscopy (PRESS) chemical-shift sequences. Assessment Median PDFF was calculated in the liver and hind limbs. [1-13 C]pyruvate dynamic MRS in the liver was quantified by the time-to-peak (TTP) for each metabolite. Animals were euthanized and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity. Statistical tests Unpaired Student's t-tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. Results Life-long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. Data conclusion PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life-long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD-exposed livers. Level of evidence 2 TECHNICAL EFFICACY STAGE: 1.

After almost 40 years since the first-ever magnetic resonance imaging (MRI) of the prostate has been made the technology has made significant strides forward: dynamic contrast-enhanced imaging, diffusion weighted imaging and MR spectroscopy being a few among the others. Moreover, the development of high power magnets and phased array coils had contributed to the drastically improved quality of the imaging. These improvements have increased the detection quality for the clinically significant prostate cancer (PCa) and early recurrences, enabling physicians to create a more personalized treatment plan easier and quicker. PROMIS (the Patient-Reported Outcome Measurement Information System) 2017 and PRECISION (Prostate Evaluation for Clinically Important Disease: Sampling Using Image Guidance or Not) 2018 studies underline the importance of MRI in detecting clinically significant PCa and avoiding overly aggressive diagnostic of clinically insignificant PCa. A large number of articles devoted to analyzing the role of MRI in diagnosing PCa (localization and staging) do not come to a uniform conclusion. This can be, in part, explained by the different study designs and protocols, as well as other controllable factors in the MRI studies themselves. The goal of this article is to attempt to analyze the role of MRI in diagnosing PCa since its advent, through its' current stage of development, as well as to explore the forward looking scenarios and opportunities for this extremely useful imaging modality.

Background Epilepsy is known to be associated with Tay-Sachs disease (TSD); however, no detailed reports are available. This case report aimed to present the clinical features of late onset spasms (LOS) in a patient with infantile TSD, and to elucidate the pathophysiology leading to LOS, using proton magnetic resonance spectroscopy (MRS). Case presentation At 11 months old, our patient had an afebrile seizure. At 14 months, he showed developmental stagnation and an increase in the frequency of epileptic seizures. Magnetic resonance imaging (T2-weighted images) showed high signal intensities in the thalamus bilaterally, and in the head of the caudate nucleus. Serum β-hexosaminidase enzyme activity was reduced, and he was diagnosed with TSD with a homozygous pathogenic variant of the HEXA gene (c. 571–1 G > T [IVS5, −1 G > T]), confirmed using direct sequence analysis. At 20 months, epileptic spasms in series around times of drowsiness and waking were observed on long-term video-electroencephalogram monitoring, in which ictal findings were different from those of startle seizures and non-epileptic myoclonus. Therefore, the epilepsy was classified as LOS. Epileptic spasms stopped following adrenocorticotropic hormone therapy, after which his vitality and consciousness improved. Serial MRS results showed a progressive decline in N-acetyl aspartate, and an increase in myoinositol in the grey matter over time. Discussion and conclusion Our patient’s MRS results suggested that cortical and subcortical axonal and neuronal degeneration with widespread gliosis in the cerebrum might lead to the development of LOS, and that LOS might be underestimated in patients with TSD.

It is essential to be aware of widely accepted criteria for grading of treatment response in both high-grade and low-grade gliomas. These criteria primarily take into account responses of measurable and nonmeasurable lesions on T2-weighted, fluid-attenuated inversion recovery, and postcontrast images to determine a final category of response for the patient. The additional role that other advanced imaging techniques, such as diffusion and perfusion imaging, can play in the surveillance of these tumors is discussed in this article.

Rapamycin (RAPA) is found to have neuro-protective properties in various neuroinflammatory pathologies, including brain aging. With magnetic resonance imaging (MRI) techniques, we investigated the effect of RAPA in a lipopolysaccharide (LPS)-induced inflammaging model in rat brains. Rats were exposed to saline (control), or LPS alone or LPS combined with RAPA treatment (via food over 6 weeks). Arterial spin labeling (ASL) perfusion imaging was used to measure relative cerebral blood flow (rCBF). MR spectroscopy (MRS) was used to measure brain metabolite levels. Contrast-enhanced MRI (CE-MRI) was used to assess blood-brain barrier (BBB) permeability. Immunohistochemistry (IHC) was used to confirm neuroinflammation. RAPA restored NF-κB and HIF-1α to normal levels. RAPA was able to significantly restore rCBF in the cerebral cortex post-LPS exposure (p < 0.05), but not in the hippocampus. In the hippocampus, RAPA was able to restore total creatine (Cr) acutely, and N-acetyl aspartate (NAA) at 6 weeks, post-LPS. Myo-inositol (Myo-Ins) levels were found to decrease with RAPA treatment acutely post-LPS. RAPA was also able to significantly restore the BBB acutely post-LPS in both the cortex and hippocampus (p < 0.05 for both). RAPA was found to increase the percent change in BOLD signal in the cortex at 3 weeks, and in the hippocampus at 6 weeks post-LPS, compared to LPS alone. RAPA treatment also restored the neuronal and macro-vascular marker, EphB2, back to normal levels. These results indicate that RAPA may play an important therapeutic role in inhibiting neuroinflammation by normalizing brain vascularity, BBB, and some brain metabolites, and has a high translational capability.

Brain lesions caused by Cryptococcus neoformans or C. gattii (cryptococcomas) are typically difficult to diagnose correctly and treat effectively, but rapid differential diagnosis and treatment initiation are crucial for good outcomes. In previous studies, cultured cryptococcal isolates and ex vivo lesion material contained high concentrations of the virulence factor and fungal metabolite trehalose. Here, we studied the in vivo metabolic profile of cryptococcomas in the brain using magnetic resonance spectroscopy (MRS) and assessed the relationship between trehalose concentration, fungal burden, and treatment response in order to validate its suitability as marker for early and noninvasive diagnosis and its potential to monitor treatment in vivo. We investigated the metabolites present in early and late stage cryptococcomas using in vivo 1H MRS in a murine model and evaluated changes in trehalose concentrations induced by disease progression and antifungal treatment. Animal data were compared to 1H and 13C MR spectra of Cryptococcus cultures and in vivo data from 2 patients with cryptococcomas in the brain. In vivo MRS allowed the noninvasive detection of high concentrations of trehalose in cryptococcomas and showed a comparable metabolic profile of cryptococcomas in the murine model and human cases. Trehalose concentrations correlated strongly with the fungal burden. Treatment studies in cultures and animal models showed that trehalose concentrations decrease following exposure to effective antifungal therapy. Although further cases need to be studied for clinical validation, this translational study indicates that the noninvasive MRS-based detection of trehalose is a promising marker for diagnosis and therapeutic follow-up of cryptococcomas.

Magnetic resonance spectroscopy (MRS), being able to identify and measure some brain components (metabolites) in pathologic lesions and in normal-appearing tissue, offers a valuable additional diagnostic tool to assess several pediatric neurological diseases. In this review we will illustrate the basic principles and clinical applications of brain proton (H(1); hydrogen) MRS (H(1)MRS), by now the only MRS method widely available in clinical practice. Performing H(1)MRS in the brain is inherently less complicated than in other tissues (e.g., liver, muscle), in which spectra are heavily affected by magnetic field inhomogeneities, respiration artifacts, and dominating signals from the surrounding adipose tissues. H(1)MRS in pediatric neuroradiology has some advantages over acquisitions in adults (lack of motion due to children sedation and lack of brain iron deposition allow optimal results), but it requires a deep knowledge of pediatric pathologies and familiarity with the developmental changes in spectral patterns, particularly occurring in the first two years of life. Examples from our database, obtained mainly from a 1.5 Tesla clinical scanner in a time span of 15 years, will demonstrate the efficacy of H(1)MRS in the diagnosis of a wide range of selected pediatric pathologies, like brain tumors, infections, neonatal hypoxic-ischemic encephalopathy, metabolic and white matter disorders.

Magnetic resonance imaging (MRI) findings of acute metabolic crisis in maple syrup urine disease (MSUD) in neonates were reviewed. This case cohort study included six MSUD neonates imaged during acute metabolic decompensation. Specific diffusion imaging and proton spectroscopic findings were reviewed. All patients revealed extensive intramyelinic cytotoxic edema typically involving myelinated white matter structures. Brainstem, cerebellar white matter and peduncles, midbrain, posterior limbs of internal capsules, central portions of periventricular, and perirolandic white matter regions showed typical MSUD edema. Gray matter structures such as dentate nucleus and thalamus were involved in all patients. Involvement of other deep nuclei was also noted in a few patients. None of the patients showed involvement of the superficial cortex. Reduction in N-acetyl aspartate, a prominent lactate peak, and a peak representing methyl groups of amino acids were characteristic findings seen on intermediate short echo time MR spectroscopy. Our case series outlines the importance of diffusion and spectroscopy MR techniques in the diagnosis of acute neonatal MSUD metabolic crisis.

The authors present an atypical case of presumed stroke-like migraine attacks after radiation therapy (SMART) syndrome in the brainstem. A 29-year-old male, who had been treated with resection and subsequent craniospinal radiation for posterior fossa medulloblastoma 21 years before, presented with subacute progressive left hemiparesis evolving over 4 days. Hematological findings, cerebrospinal fluid (CSF), and electroencephalogram (EEG) were unremarkable. Magnetic resonance imaging (MRI) showed a round area of hyperintense FLAIR signal centered within the pons associated with central restricted diffusion, peripheral enhancement, and small paramagnetic low susceptibility signal foci consistent with petechial hemorrhage. Positron emission tomography (PET), perfusion MRI, and MR spectroscopy revealed no evidence of tumor recurrence. The diagnosis of SMART syndrome is presumed from the conventional and advanced imaging findings, clinical history, and clinical course.

In this review, we provide the data on the modern use of different MRI modalities and computer tomography (CT) as diagnostic and prognostic tools for meningitis of various etiology, first of all, bacterial purulent meningitis. Each of these techniques has its own field of application depending on the stage of the disease and the patients condition (necessity of intensive care procedures, ventilation support). The opinions on the diagnostic value of CT and structural MRI data differ and depend on the etiology and phase of the inflammatory process. In the recent years, the techniques of multiparametric MRI are widely implemented in the practice. Beside structural MRI, they include diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI) and MR spectroscopy (MRS), as well as studies with artificial contrast; there are some reports that these modalities are more effective as a diagnostic tool in meningitis. Thus, the use of multiparametric MRI techniques and CT with contrast is promising and justified for the diagnostics of patients with bacterial purulent meningitis from the viewpoint of enhanced sensitivity.

Magnetic resonance imaging (MRI) is a versatile imaging modality utilized in various medical fields. Specifically used for evaluation of soft tissues, with non-ionizing radiation and multiplanar sections that has provided great guidance to diagnosis. Nowadays, use of MRI in dental practice is becoming more pervasive, especially for the evaluation of head-and-neck cancer, detection of salivary gland lesions, lymphadenopathy, and temporomandibular joint disorders. Understanding the basic principles, its recent advances, and multiple applications in dentomaxillofacial region helps significantly in the diagnostic decision making. In this article, the principle of MRI and its recent advances are reviewed, with further discussion on the appearance of various maxillofacial pathosis.

Introduction. Conventional MR imaging provides highly detailed anatomic information with unrivalled soft tissue contrast making it the mainstay in the diagnosis of suspected brain lesions. Despite this, MRI alone at times cannot answer the diagnostic questions in quite a few patients. Proton MR Spectroscopy (H-MRS) provides information on the metabolic composition within an area under interrogation. By comparing the relative concentrations of specific metabolites, the neuroradiologist can deduce critical information regarding neuronal cell density and integrity, cell membrane turnover, metabolic fuel, and possible necrosis in the region of interest. This provides a biochemical picture of the underlying pathology and thus aids in the diagnosis. Methods. This was a cross-sectional comparative study. Results. Of the 63 patients examined by MRI and MRS for intracranial mass lesions, the radiologists were able to offer a single imaging diagnosis based on MRI alone in only 15 patients (23.8%) while when MRI imaging was combined with MR spectroscopy, a single imaging diagnosis was offered in 47 patients (74.6%). This was an overall statistically significant improvement. Conclusion. MRS aided the radiologist in offering a single diagnosis in high versus low-grade gliomas, high-grade gliomas versus tuberculomas, and recurrent tumours versus radiation necrosis.

The diagnosis of amyotrophic lateral sclerosis (ALS) requires both upper and lower motor neuron signs. However, quite a few patients with ALS lack the upper motor neuron sign during the disease. This study sought to investigate whether metabolites, including glutamate (Glu), N-acetyl aspartate (NAA), and gamma aminobutyric acid (GABA), in the supplementary motor area (SMA) measured by magnetic resonance spectroscopy (MRS), could be a surrogate biomarker for ALS. Twenty-five patients with ALS and 12 controls underwent 3.0-T MR scanning, which measured Glu, NAA, and GABA. Finally, receiver operating characteristic (ROC) curves were created and the area under curve (AUC) was calculated to assess the diagnostic power. Logistic regression analysis revealed the usefulness of both Glu and NAA for the differentiation of ALS from controls (Glu, P = 0.009; NAA, P = 0.033). The ratio of Glu to NAA or GABA was significantly increased in patients with ALS (Glu/NAA, P = 0.027; Glu/GABA, P = 0.003). Both the AUCs were more than 0.7, with high specificity but low sensitivity. The present findings might indicate that both the Glu/NAA and the Glu/GABA ratios in the SMA could be potential biomarkers for the diagnosis of ALS.

CLN3 disease is a pediatric neurodegenerative condition wherein seizures are common. The most common disease-causing variant is an ~1-kb deletion in CLN3. We investigated seizure phenotype in relation to genotype and to adaptive behavior, MR spectroscopy and CSF biochemical markers in a CLN3 cohort. We performed seizure phenotyping using clinical history, EEG, and the Unified Batten Disease Rating Scale (UBDRS) seizure score. We assessed correlations of seizure severity with disease severity (UBDRS capability), adaptive behavior composite score (ABC; Vineland-3), glutamate+glutamine+GABA and N-acetylaspartate+N-acetylaspartyl glutamate (MR spectroscopy), and CSF neurofilament light chain (NEFL) levels. In 20 participants, median age was 10.7 years (IQR = 7.8). Eighteen completed baseline EEG; 12 had a 1-year follow-up. Seizures were reported in 14 (8 1-kb deletion homozygotes), with median age at onset of 10.0 (IQR = 6.8). Epileptiform discharges were noted in 15 (9 homozygotes). Bilateral tonic clonic (n = 11) and nonmotor seizures (n = 7) were most common. UBDRS seizure score correlated with age (rp = 0.50; [0.08,0.77]; P = .02), UBDRS capability (rp = -0.57; [-0.81,-0.17]; P = .009) and ABC (rp = -0.66; [-0.85,-0.31]; P = .001) scores, glutamate+glutamine+GABA (rp = -0.54; [-0.80,-0.11]; P = .02) and N-acetylaspartate+N-acetylaspartyl glutamate (rp = -0.54; [-0.80,-0.11]; P = .02), and CSF NEFL (rp = 0.65; [0.29,0.85]; P = .002) levels. After controlling for age, correlations with ABC and CSF NEFL remained significant. In our CLN3 cohort, seizures and epileptiform discharges were frequent and often started by age 10 years without significant difference between genotypes. ABC and CSF NEFL correlate with UBDRS seizure score, reflecting the role of seizures in the neurodegenerative process. Longitudinal evaluations in a larger cohort are needed to confirm these findings.

Several clinical upper motor neuron burden scales (UMNSs) variably measure brain dysfunction in amyotrophic lateral sclerosis (ALS). Here, we compare relationship of two widely used clinical UMNSs in ALS (Penn and MGH UMNSs) with (a) neuroimaging markers of brain dysfunction and (b) neurological impairment status using the gold-standard functional measure, the revised ALS Functional Rating Scale (ALSFRS-R). MGH UMNS measures hyperreflexia alone, and Penn UMNS measures hyperreflexia, spasticity, and pseudobulbar affect. Twenty-eight ALS participants underwent both Penn and MGH UMNSs, at a matching time-point as a simultaneous [11C]PBR28 positron emission tomography (PBR28-PET)/Magnetic Resonance scan and ALSFRS-R. The two UMNSs were compared for localization and strength of association with neuroimaging markers of: (a) neuroinflammation, PBR28-PET and MR Spectroscopy metabolites (myo-inositol and choline) and (b) corticospinal axonal loss, fractional anisotropy (FA), and MR Spectroscopy metabolite (N-acetylaspartate). Among clinical UMN manifestations, segmental hyperreflexia, spasticity, and pseudobulbar affect occurred in 100, 43, and 18% ALS participants, respectively. Pseudobulbar affect did not map to any specific brain regional dysfunction, while hyperreflexia and spasticity subdomains significantly correlated and colocalized neurobiological changes to corticospinal pathways on whole brain voxel-wise analyses. Both UMNS total scores showed significant and similar strength of association with (a) neuroimaging changes (PBR28-PET, FA, MR Spectroscopy metabolites) in primary motor cortices and (b) severity of functional decline (ALSFRS-R). Hyperreflexia is the most frequent clinical UMN manifestation and correlates best with UMN molecular imaging changes in ALS. Among Penn UMNS's subdomains, hyperreflexia carries the weight of association with neuroimaging markers of biological changes in ALS. A clinical UMN scale comprising hyperreflexia items alone is clinically relevant and sufficient to predict the highest yield of molecular neuroimaging abnormalities in ALS.

Despite intensive research, brain tumors are amongst the malignancies with the worst prognosis; therefore, a prompt diagnosis and thoughtful assessment of the disease is required. The resistance of brain tumors to most forms of conventional therapy has led researchers to explore the underlying biology in search of new vulnerabilities and biomarkers. The unique metabolism of brain tumors represents one potential vulnerability and the basis for a system of classification. Profiling this aberrant metabolism requires a method to accurately measure and report differences in metabolite concentrations. Magnetic resonance-based techniques provide a framework for examining tumor tissue and the evolution of disease. Nuclear Magnetic Resonance (NMR) analysis of biofluids collected from patients suffering from brain cancer can provide biological information about disease status. In particular, urine and plasma can serve to monitor the evolution of disease through the changes observed in the metabolic profiles. Moreover, cerebrospinal fluid can be utilized as a direct reporter of cerebral activity since it carries the chemicals exchanged with the brain tissue and the tumor mass. Metabolic reprogramming has recently been included as one of the hallmarks of cancer. Accordingly, the metabolic rewiring experienced by these tumors to sustain rapid growth and proliferation can also serve as a potential therapeutic target. The combination of 13C tracing approaches with the utilization of different NMR spectral modalities has allowed investigations of the upregulation of glycolysis in the aggressive forms of brain tumors, including glioblastomas, and the discovery of the utilization of acetate as an alternative cellular fuel in brain metastasis and gliomas. One of the major contributions of magnetic resonance to the assessment of brain tumors has been the non-invasive determination of 2-hydroxyglutarate (2HG) in tumors harboring a mutation in isocitrate dehydrogenase 1 (IDH1). The mutational status of this enzyme already serves as a key feature in the clinical classification of brain neoplasia in routine clinical practice and pilot studies have established the use of in vivo magnetic resonance spectroscopy (MRS) for monitoring disease progression and treatment response in IDH mutant gliomas. However, the development of bespoke methods for 2HG detection by MRS has been required, and this has prevented the wider implementation of MRS methodology into the clinic. One of the main challenges for improving the management of the disease is to obtain an accurate insight into the response to treatment, so that the patient can be promptly diverted into a new therapy if resistant or maintained on the original therapy if responsive. The implementation of 13C hyperpolarized magnetic resonance spectroscopic imaging (MRSI) has allowed detection of changes in tumor metabolism associated with a treatment, and as such has been revealed as a remarkable tool for monitoring response to therapeutic strategies. In summary, the application of magnetic resonance-based methodologies to the diagnosis and management of brain tumor patients, in addition to its utilization in the investigation of its tumor-associated metabolic rewiring, is helping to unravel the biological basis of malignancies of the central nervous system.

We characterize the whole-brain N-acetyl-aspartate (WBNAA) and brain tissue fractions across the adult lifespan and test the hypothesis that, despite age-related atrophy, neuronal integrity (reflected by WBNAA) is preserved in normal aging. Two-hundred-and-seven participants: 133 cognitively intact older adults (73.6 ± 7.4 mean ± standard deviation, range: 60–90 year old) and 84 young (37.9 ± 11, range: 21–59 year old) were scanned with proton magnetic resonance spectroscopy and T1-weighted MRI. Their WBNAA, fractional brain parenchyma, and gray and white matter volumes (fBPV, fGM, and fWM) were compared and modeled as functions of age and sex. Compared with young, older-adults’ WBNAA was lower by ~35%, and fBPV, fGM and fWM were lower by ~10%. Linear regressions found 0.5%/year WBNAA and 0.2%/year fBPV and fGM declines, whereas fWM rose to age ~40 years, and declined thereafter. fBPV and fGM were 1.8% and 4% higher in women, with no sex decline rates difference. We conclude that contrary to our hypothesis, atrophy was accompanied by WBNAA decline. Across the entire age range, women's brains showed less atrophy than men's. Formulas to estimate WBNAA and brain tissue fractions in healthy adults are provided to help differentiate normal from abnormal aging.

Background Polyphenols in extra virgin olive oil (EVOO) have been found to reduce the expression of PPARγ2, inhibit adipocyte differentiation, and enhance the formation of osteoblasts from bone marrow stem cells. However, the underlying mechanisms of their action remain unknown. Purpose To determine the sequential effects of EVOO on marrow fat expansion induced by estrogen deprivation using 3.0-T proton magnetic resonance (MR) spectroscopy in an ovariectomy (OVX) rabbit model of postmenopausal bone loss over a six-month period. Material and Methods A total of 45 female New Zealand rabbits were equally divided into sham-operation, OVX controls, and OVX treated with EVOO for six months. Marrow fat fraction was measured by MR spectroscopy at baseline conditions, and three and six months postoperatively, respectively. Serum bone biomarkers, lumbar and femoral bone mineral density, microtomographic parameters, biomechanical properties, and quantitative parameters of marrow adipocytes were studied. Results OVX was associated with marrow adiposity in a time-dependent manner, accompanied with increased bone turnover and impaired bone mass and trabecular microarchitecture. In OVX rabbits, EVOO markedly alleviated trabecular bone loss and reduced the accumulation of lipid droplets including adipocyte size, density, and areas of fat deposits in the bone marrow. EVOO prevented such changes in terms of both marrow adiposity and bone remodeling. Conclusion Early EVOO treatment may exert beneficial effects on bone by modulating marrow adiposity, which would support their protective effect against bone pathologies.

Purpose This study develops a tracer kinetic model of xenon uptake in the human brain to determine the transfer rate of inhaled hyperpolarized 129 Xe from cerebral blood to gray matter that accounts for the effects of cerebral physiology, perfusion and magnetization dynamics. The 129 Xe transfer rate is expressed using a tracer transfer coefficient, which estimates the quantity of hyperpolarized 129 Xe dissolved in cerebral blood under exchange with depolarized 129 Xe dissolved in gray matter under equilibrium of concentration. Theory and methods Time-resolved MR spectra of hyperpolarized 129 Xe dissolved in the human brain were acquired from three healthy volunteers. Acquired spectra were numerically fitted with five Lorentzian peaks in accordance with known 129 Xe brain spectral peaks. The signal dynamics of spectral peaks for gray matter and red blood cells were quantified, and correction for the 129 Xe T1 dependence upon blood oxygenation was applied. 129 Xe transfer dynamics determined from the ratio of the peaks for gray matter and red blood cells was numerically fitted with the developed tracer kinetic model. Results For all the acquired NMR spectra, the developed tracer kinetic model fitted the data with tracer transfer coefficients between 0.1 and 0.14. Conclusion In this study, a tracer kinetic model was developed and validated that estimates the transfer rate of HP 129 Xe from cerebral blood to gray matter in the human brain.

Background:Matrix-associated autologous chondrocyte implantation (MACI) with autologous bone grafting (ABG) is an effective surgical treatment for osteochondral defects. Quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as noninvasive biomarkers to assess the biochemical composition of cartilage repair tissue.Purpose:To evaluate the association of quantitative MRI parameters of cartilage repair tissue and subchondral bone marrow with magnetic resonance morphologic and clinical outcomes after MACI with ABG of the knee.Study Design:Case series; Level of evidence, 4.Methods:Qualitative and quantitative 3 T MRI of the knee was performed in 21 patients (16 male) at 2.5 years after MACI with ABG at the medial (18/21) or lateral (3/21) femoral condyle for the treatment of osteochondral defects. Morphologic MRI sequences were assessed using MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 scores. T2 relaxation time measurements for the assessment of cartilage repair tissue (CRT2) were obtained. Single-voxel magnetic resonance spectroscopy was performed in underlying subchondral bone marrow (BM) and at both central femoral condyles. The presence of pain and Tegner scores were noted. Statistical analyses included Student t tests, correlation analyses, and multivariate regression models.Results:The mean defect size was 4.9 ± 1.9 cm2. At a follow-up of 2.5 ± 0.3 years, 9 of 21 patients were asymptomatic. Perfect defect filling was achieved in 66.7% (14/21) of patients. MOCART 2.0 scores (74.1 ± 18.4) did not indicate pain (68.3 ± 19.0 [pain] vs 81.7 ± 15.4 [no pain]; P = .102). However, knee pain was present in 85.7% (6/7) of patients with deep bony defects (odds ratio, 8.0; P = .078). Relative CRT2 was higher in hypertrophic cartilage repair tissue than in repair tissue with normal filling (1.54 ± 0.42 vs 1.13 ± 0.21, respectively; P = .022). The underlying BM edema–like lesion (BMEL) volume was larger in patients with underfilling compared with patients with perfect defect filling (1.87 ± 1.32 vs 0.31 ± 0.51 cm3, respectively; P = .002). Patients with severe pain showed a higher BMEL volume (1.2 ± 1.3 vs 0.2 ± 0.4 cm3, respectively; P = .046) and had a higher BM water fraction (26.0% ± 12.3% vs 8.6% ± 8.1%, respectively; P = .026) than did patients without pain.Conclusion:Qualitative and quantitative MRI parameters including the presence of subchondral defects, CRT2, BMEL volume, and BM water fraction were correlated with cartilage repair tissue quality and clinical symptoms. Therefore, the integrity of subchondral bone was associated with outcomes after osteochondral transplantation.