Antaros Medical (Sweden)

Background/Objectives: Magnetisation Transfer (MT) MRI is used for neuro-degenerative disorders, including Multiple Sclerosis (MS), providing an indirect measure of large biomolecular MR signal sources which cannot be observed directly because their typical T2 is usually much shorter than the echo time (TE) of conventional MR sequences. We investigated a 3D-radial Zero Time of Echo (ZTE) MT-weighted sequence with potentially enhanced sensitivity to short-T2 MR signals indirectly (via MT weighting) and directly (due to the short TE). Methods: The sequence runs on a human 7T MR scanner, producing whole-brain MT-weighted images with isotropic 0.8 mm resolution in 6.5 minutes. One RF pulse is used to suppress the fat signal and generate MT weighting, reducing RF power deposition to moderate levels. The small excitation pulses and the “quasi-adiabatic” MT pulse mitigate the negative effects of inhomogeneous transmit RF fields observed at 7T in the human head, facilitating the generation of uniform Magnetisation Transfer Ratio (MTR) maps. Results: Results from a biologic phantom, a healthy volunteer, and an MS patient illustrate important imaging features of the “SilentMT” sequence. When the MS patient images were compared with Fluid Attenuated Inversion Recovery (FLAIR) images taken on the same patient at 1.5T and 7T, SilentMT was able to detect all the MS lesions observed on the “reference truth” 1.5T FLAIR; 7T FLAIR, however, failed to detect some lesions in the temporal lobe and brain stem. SilentMT detected a lesion which was not immediately apparent on either FLAIR image. Increased MTR was observed in some regions of the brain of the MS patient, notably the left temporal lobe. Conclusions: This initial investigation of an MT-weighted ZTE sequence shows evidence that it may be more sensitive to pathology in a patient with MS.

ABSTRACTBackground and AimsThe relationship between skeletal muscle features and hepatic fat infiltration remains understudied. To address this knowledge gap, a cross‐sectional observational study was conducted using data from two ancillary studies of the SCAPIS cohort.MethodThe study aimed to examine the relationship between skeletal thigh muscle radiodensity (Hounsfield Units, HU) and area (cm2), and metabolic dysfunction‐associated steatotic liver disease (MASLD) and hepatic radiodensity (HU). Multivariable linear regression analyses were applied to data from 4620 participants (52% women) with a mean age of 57.9 years. Adjustments for confounders were computed in four theoretical models.ResultsResults showed a positive significant association between thigh muscle area and MASLD (OR = 1.29, 95% CI 1.02, 1.62, p = 0.033), and a negative association with hepatic radiodensity (B = −0.76, 95% CI −1.19, −0.34, p = 0.001), independent of muscle radiodensity. Additionally, a significant association was observed between muscle radiodensity and hepatic radiodensity (B = 0.37, 95% 0.09, 0.64, p = 0.008). Finally, sex differences were notable in the association between thigh muscle area and MASLD (F‐test = 0.10). Specifically, we observed statistically significant associations between thigh muscle features and liver density/MASLD in men, but not in women.ConclusionConclusively, increased thigh muscle volume was associated with greater odds of MASLD and hepatic steatosis, independent of muscle radiodensity. Yet, greater thigh muscle radiodensity was associated with decreased odds of hepatic steatosis, regardless of the muscle volume. Furthermore, a sex difference was observed in our study, underscoring the importance of considering sex‐specific factors on the development of MASLD.

Funding Agencies|European Research Council [ERC-STG-2018-801965]; Swedish Research Council [VR 2019-01471, 2019-01236]; Swedish Heart-Lung Foundation [Hjart-Lungfonden] [20190505, 20200173]; Swedish Government [ALFGBG-991828]; Swedish county councils, the ALF-agreement [ALFGBG-991828]

Genetic variants associated with increased liver fat and volume have been reported, but whether physical activity (PA) can attenuate the impact of genetic susceptibility to these traits is poorly understood. We aimed to investigate whether higher PA modify genetic impact on liver-related traits in the UK Biobank cohort. PA was self-reported, while magnetic resonance images were used to estimate liver fat (n = 27,243) and liver volume (n = 24,752). Metabolic dysfunction-associated liver disease (MASLD) and chronic liver disease (CLD) were diagnosed using ICD-9 and ICD-10 codes. Ten liver fat and eleven liver volume-associated genetic variants were selected and unweighted genetic-risk scores for liver fat (GRSLF) and liver volume (GRSLV) were computed. Linear regression analyses were performed to explore interactions between GRSLF/ GRSLV and PA in relation to liver-related traits. Association between GRSLF and liver fat was not different among lower (β = 0.063, 95% CI 0.041–0.084) versus higher PA individuals (β = 0.065, 95% CI 0.054–0.077, pinteraction = 0.62). The association between the GRSLV and liver volume was not different across different PA groups (pinteraction = 0.71). Similarly, PA did not modify the effect of GRSLF and GRSLV on MASLD or CLD. Our findings show that physical activity and genetic susceptibility to liver-related phenotypes seem to act independently, benefiting all individuals regardless of genetic risk.

PreambleThe Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging.The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized.These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI, the ISMRM, and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question.The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines.The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment.Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

Chronic kidney disease (CKD) associated with diabetes mellitus (DM) (known as diabetic kidney disease, DKD) is a serious and growing healthcare problem worldwide. In DM patients, DKD is generally diagnosed based on the presence of albuminuria and a reduced glomerular filtration rate. Diagnosis rarely includes an invasive kidney biopsy, although DKD has some characteristic histological features, and kidney fibrosis and nephron loss cause disease progression that eventually ends in kidney failure. Alternative sensitive and reliable non-invasive biomarkers are needed for DKD (and CKD in general) to improve timely diagnosis and aid disease monitoring without the need for a kidney biopsy. Such biomarkers may also serve as endpoints in clinical trials of new treatments. Non-invasive magnetic resonance imaging (MRI), particularly multiparametric MRI, may achieve these goals. In this article, we review emerging data on MRI techniques and their scientific, clinical, and economic value in DKD/CKD for diagnosis, assessment of disease pathogenesis and progression, and as potential biomarkers for clinical trial use that may also increase our understanding of the efficacy and mode(s) of action of potential DKD therapeutic interventions. We also consider how multi-site MRI studies are conducted and the challenges that should be addressed to increase wider application of MRI in DKD.

Abstract Background and Aims We recently showed that comprehensive non-contrast multiparametric Magnetic Resonance Imaging (mpMRI) allowed functional and structural assessment of diabetic kidney disease (DKD) and that an imaging endpoint, R1 cortex, showed significant predictive property for progression of DKD. We further investigated the performance of other MRI and lab biomarkers for predicting disease progression. Method In this prospective study, 38 DKD subjects aged 18–79 years and 20 age- and gender-matched healthy volunteers (HV) were included at baseline. 31 DKD subjects (2 stage 2, 13 stage 3, 14 stage 4, and 2 stage 5) and 17 HV were re-examined at 2 years ± 6 months. Clinical and lab examination, iohexol clearance for measured glomerular filtration rate (mGFR), urine albumin:creatinine ratio (UACR) and mpMRI were performed at both visits. A wide range of MRI biomarkers associated with kidney hemodynamics, oxygenation and macro/microstructure were included for evaluation. Disease progression was defined by at least one of the following at 2 years: decrease in mGFR slope of >5 mL/year/1.73 m2; worsening UACR category; or any major adverse kidney event defined as sustained decrease in eGFR of >40%; doubling of serum creatinine from baseline; development of kidney failure with mGFR <15 ml/min/1.73 m2; or death from renal cause. Univariable logistic regression analyses were performed to discriminate between progressors and non-progressors using each relevant lab and imaging endpoint as a predictor variable. Results Mean 2-year mGFR decline (ml/min/1.73 m2) in DKD patients was -2.7± 5.4 and in HV -1.9 ± 10.7. 13/31 (42%) DKD subjects and 4/17 (24%) HV progressed. Key lab biomarkers are shown in Table 1 and MRI biomarkers in Table 2. Conclusion Of all analyzed biomarkers, only the imaging biomarker R1 cortex, which reflects molecular environment viscosity, fibrosis, and inflammation (interstitial oedema, cellular swelling) showed significant predictive property for progression of DKD. UACR trended towards significance but was not statistically significant. R1 cortex outperformed all other imaging and lab biomarkers, but further studies with R1 cortex as a pre-specified endpoint are required to confirm these results.

Biomedical imaging techniques like positron emission tomography (PET) have been implemented into the clinical diagnostic routine in many areas, such as oncology, neurology, and cardiology. However, their use in the clinical management of diabetes is not as advanced. Recent decades have seen progress in novel techniques for clinical molecular imaging of receptors and cell subtypes, including those crucial for pancreatic function in both health and disease. Advances include studying, e.g., the insulin-producing beta cells and the most common incretin and gut hormone receptors. Techniques for efficient functionalisation and radiolabelling of peptides and proteins have enabled PET imaging using the growing number of biological drugs or modified endogenous hormones. Importantly, the novel techniques are in or under clinical translation and approval, suggesting that they may become part of the routine assessment in diabetes diagnosis and management in the coming years. This chapter summarises recent developments and advances in the application of PET techniques for visualising processes in the pancreas that are crucial in diabetes pathology and treatment.

Lower SED time is associated with better hepatic health independently of MVPA. Reducing SED time might be a first step in the management of pediatric obesity NAFLD when increasing MVPA is not possible. •MVPA and SED times are associated with cardiometabolic risks in youths with obesity. • The relationships between NAFLD markers and concomitant MVPA and SED times have not been studied in this population. •Low SED time is associated with healthier liver enzyme profiles and LFC independent of MVPA. • While low SED/high MVPA is the more desirable pattern, low SED/low MVPA pattern would have healthier liver enzyme profile compared with high MVPA/high SED, independent of BMI, suggesting that reducing SED time irrespective of MVPA is needed to optimize liver health.

Fatty acids (e.g. 16:1n-7) and desaturase indices (e.g. stearoyl-CoA desaturase, SCD) in plasma cholesteryl esters (CE) and phospholipids (PL) are used as biomarkers of dietary fat quality and lipid metabolism and are associated with disease outcomes. Endogenously produced circulating fatty acids are believed to reflect composition of the liver, yet little data exist to support such relationship. We investigated associations between circulating fatty acids and fatty acids within the liver. Liver biopsies and blood were collected from n=60 patients with non-alcoholic fatty liver disease. Fatty acids in CE, PL and triglycerides (TG) in plasma and liver were analyzed using gas chromatography. Associations were assessed using Spearman rank correlations. Overall, fatty acids and desaturase indices in plasma PL and TG showed moderate-strong correlations with fatty acids and desaturase indices in corresponding lipid fractions in liver. For plasma CE, 16:1n-7 and SCD were correlated with 16:1n-7 and SCD in liver CE. Noteworthy, fatty acids in plasma CE and PL also showed moderate-strong correlations with fatty acids in liver TG (e.g. r=0.82-0.87 for 16:1n-7 and r=0.77 for SCD). We demonstrate that fatty acids in circulating lipid fractions, including CE, TG and PL, reflects the composition of liver TG in humans, suggesting that circulating fatty acids might be useful biomarkers for the fatty acid composition of the liver. As liver tissue is rarely available in cohort studies, our findings could enhance our understanding of plasma fatty acids as markers of hepatic lipid metabolism and their links to metabolic diseases.