To investigate the pathophysiology of fatigue in MS, we assessed cerebral glucose metabolism (CMR-Glu) in 47 MS patients using PET and 18F-fluorodeoxyglucose. Applying the Fatigue Severity Scale (FSS), we first compared MS patients with severe fatigue (MS-FAT, n = 19, FSS > 4.9) and MS patients without fatigue (MS-NOF, n = 16, FSS < 3.7) on a pixel-by-pixel basis using Statistical Parametric Mapping (SPM95). Second, we compared FSS values of all 47 patients covering the whole range of this scale with CMRGlu using an analysis of covariance (SPM95). In addition, we determined global CMRGlu by region-of-interest analysis. Sixteen healthy subjects served as control subjects (CON). Global CMRGlu was significantly lower in both MS groups compared with CON (CON 43.3 +/- 6.9 mumol/100 mL/min, MS-FAT 34.7 +/- 4.4, MS-NOF 35.4 +/- 4.5) but was not related to fatigue severity. Comparing the two MS groups, SPM95 analysis revealed predominant CMRGlu reductions bilaterally in a prefrontal area involving the lateral and medial prefrontal cortex and adjacent white matter, in the premotor cortex, putamen, and in the right supplementary motor area of MS-FAT. In addition, there were CMRGlu reductions in the white matter extending from the rostral putamen toward the lateral head of the caudate nucleus. FSS values were inversely related to CMRGlu in the right prefrontal cortex. CMRGlu in the cerebellar vermis and anterior cingulate was relatively higher in MS-FAT than in MS-NOF patients. CMRGlu of both regions showed positive correlations with FSS values. Our data suggest that fatigue in MS is associated with frontal cortex and basal ganglia dysfunction that could result from demyelination of the frontal white matter.

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Background-Left ventricular ejection fraction is a powerful independent predictor of survival in cardiac patients, especially those with coronary artery disease. Delayed-enhancement magnetic resonance imaging (DE-MRI) can accurately identify irreversible myocardial injury with high spatial and contrast resolution. To date, relatively limited data are available on the prognostic value of DE-MRI, so we sought to determine whether DE-MRI findings independently predict survival. Methods and Results-The medical records of 857 consecutive patients who had complete cine and DE-MRI evaluation at a tertiary care center were reviewed regardless of whether the patients had coronary artery disease. The presence and extent of myocardial scar were evaluated qualitatively by a single experienced observer. The primary, composite end point was all-cause mortality or cardiac transplantation. Survival data were obtained from the Social Security Death Index. The median follow-up was 4.4 years; 252 patients (29%) reached one of the end points. Independent predictors of mortality or transplantation included congestive heart failure, ejection fraction, and age (PϽ0.0001 for each), as well as scar index (hazard ratio, 1.26; 95% confidence interval, 1.02 to 1.55; Pϭ0.033). Similarly, in subsets of patients with or without coronary artery disease, scar index also independently predicted mortality or transplantation (hazard ratio, 1.33; 95% confidence interval, 1.05 to 1.68; Pϭ0.018; and hazard ratio, 5.65; 95% confidence interval, 1.74 to 18.3; Pϭ0.004, respectively). Cox regression analysis showed worse outcome in patients with any DE in addition to depressed left ventricular ejection fraction (Ͻ50%). Conclusion-The degree of DE detected by DE-MRI appears to strongly predict all-cause mortality or cardiac transplantation after adjustment for traditional, well-known prognosticators.

Purpose-To demonstrate feasibility of developing a noninvasive extracellular pH (pH e) mapping method on a clinical MRI scanner for molecular imaging of liver cancer. Methods-In vivo pH e mapping has been demonstrated on preclinical scanners (e.g., 9.4T, 11.7T) with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), where the pH e readout by 3D chemical shift imaging (CSI) depends on hyperfine shifts emanating from paramagnetic macrocyclic chelates like TmDOTP 5− which upon extravasation from blood resides in the extracellular space. We implemented BIRDS-based pH e mapping on a clinical 3T Siemens scanner, where typically diamagnetic 1 H signals are detected using millisecond-long radiofrequency (RF) pulses, and 1 H shifts span over ±10 ppm with long transverse (T 2 , 10 2 ms) and longitudinal (T 1 , 10 3 ms) relaxation times. We modified this 3D-CSI method for ultra-fast acquisition with microsecond-long RF pulses, because even at 3T the paramagnetic 1 H shifts of TmDOTP 5− have millisecond-long T 2 and T 1 and ultra-wide chemical shifts (±200 ppm) as previously observed in ultra-high magnetic fields. Results-We validated BIRDS-based pH in vitro with a pH electrode. We measured pH e in a rabbit model for liver cancer using VX2 tumors, which are highly vascularized and hyperglycolytic. Compared to intratumoral pH e (6.8 ± 0.1; P < 10 −9) and tumor's edge pH e (6.9 ± 0.1; P < 10 −7), liver parenchyma pH e was significantly higher (7.2 ± 0.1). Tumor localization was confirmed with histopathological markers of necrosis (hematoxylin and eosin), glucose uptake (glucose transporter 1), and tissue acidosis (lysosome-associated membrane protein 2).

Background Recent evidence shows an association between coronavirus disease 2019 (COVID-19) infection and a severe inflammatory syndrome in children. Cardiovascular magnetic resonance (CMR) data about myocardial injury in children are limited to small cohorts. The aim of this multicenter, international registry is to describe clinical and cardiac characteristics of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 using CMR so as to better understand the real extent of myocardial damage in this vulnerable cohort. Methods and results Hundred-eleven patients meeting the World Health Organization criteria for MIS-C associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), having clinical cardiac involvement and having received CMR imaging scan were included from 17 centers. Median age at disease onset was 10.0 years (IQR 7.0–13.8). The majority of children had COVID-19 serology positive (98%) with 27% of children still having both, positive serology and polymerase chain reaction (PCR). CMR was performed at a median of 28 days (19–47) after onset of symptoms. Twenty out of 111 (18%) patients had CMR criteria for acute myocarditis (as defined by the Lake Louise Criteria) with 18/20 showing subepicardial late gadolinium enhancement (LGE). CMR myocarditis was significantly associated with New York Heart Association class IV (p = 0.005, OR 6.56 (95%-CI 1.87–23.00)) and the need for mechanical support (p = 0.039, OR 4.98 (95%-CI 1.18–21.02)). At discharge, 11/111 (10%) patients still had left ventricular systolic dysfunction. Conclusion No CMR evidence of myocardial damage was found in most of our MIS-C cohort. Nevertheless, acute myocarditis is a possible manifestation of MIS-C associated with SARS-CoV-2 with CMR evidence of myocardial necrosis in 18% of our cohort. CMR may be an important diagnostic tool to identify a subset of patients at risk for cardiac sequelae and more prone to myocardial damage. Clinical trial registration: The study has been registered on ClinicalTrials.gov, Identifier NCT04455347, registered on 01/07/2020, retrospectively registered.

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Background Immune checkpoint inhibitors (ICIs) are highly effective in treating cancer; however, cardiotoxicity can occur, including myocarditis. Cardiac magnetic resonance (CMR) imaging is useful for evaluation of myocarditis, although it has not been well studied in ICI cardiotoxicity. Methods We identified patients referred for CMR evaluation of ICI cardiotoxicity from September 2015 through September 2019. We assessed structural and functional parameters, feature tracking (FT) left ventricular and atrial strain, T2- weighted ratios and quantitative late gadolinium enhancement (LGE). We also applied the Updated Lake Louise Criteria for diagnosis of myocarditis. Results Of the 20 patients referred, the median left ventricular ejection fraction (LVEF) was 52.5% ± 19.1 and 50% had a normal LVEF (≥53%). FT strain analysis revealed an average abnormal global longitudinal strain (GLS) of −9.8%± 4.2%. In patients with a normal LVEF, the average GLS remained depressed at −12.3%± 2.4%. In all patients, GLS demonstrated a significant negative correlation with LVEF (rs = −0.64, p 0.002). Sixteen patients (80%) had presence of LGE (14 non-ischemic pattern and 2 ischemic). Percent LGE did not correlate with any CMR parameters and notably did not correlate with LVEF (rs = −0.29, p = 0.22) or GLS (rs = 0.10, p = 0.67), highlighting the value of tissue characterization beyond functional assessment. Nine patients (45%) met full Updated Lake Louise Criteria and 85% met at least one criterion, suggestive of myocarditis in the correct clinical context. Thirteen patients (65%) were treated for ICI-associated myocarditis and, of these, 54% (n = 7) had recovery of LVEF to normal. There was no correlation between LVEF (p = 0.47), GLS (0.89), or % LGE (0.15) and recovery of LVEF with treatment. Conclusion In patients with suspected ICI cardiotoxicity, CMR is an important diagnostic tool, even in the absence of overt left ventricular dysfunction, as abnormalities in left ventricular strain, T2 signal and LGE can identifying disease.