Low-dose acetylsalicylic acid reduces local inflammation and tissue perfusion in dense breast tissue in postmenopausal women.

PURPOSE: One major risk factor for breast cancer is high mammographic density. It has been estimated that dense breast tissue contributes to ~ 30% of all breast cancer. Prevention targeting dense breast tissue has the potential to improve breast cancer mortality and morbidity. Anti-estrogens, which may be associated with severe side-effects, can be used for prevention of breast cancer in women with high risk of the disease per se. However, no preventive therapy targeting dense breasts is currently available. Inflammation is a hallmark of cancer. Although the biological mechanisms involved in the increased risk of cancer in dense breasts is not yet fully understood, high mammographic density has been associated with increased inflammation. We investigated whether low-dose acetylsalicylic acid (ASA) affects local breast tissue inflammation and/or structural and dynamic changes in dense breasts. METHODS: Postmenopausal women with mammographic dense breasts on their regular mammography screen were identified. A total of 53 women were randomized to receive ASA 160 mg/day or no treatment for 6 months. Magnetic resonance imaging (MRI) was performed before and after 6 months for a sophisticated and continuous measure breast density by calculating lean tissue fraction (LTF). Additionally, dynamic quantifications including tissue perfusion were performed. Microdialysis for sampling of proteins in vivo from breasts and abdominal subcutaneous fat, as a measure of systemic effects, before and after 6 months were performed. A panel of 92 inflammatory proteins were quantified in the microdialysates using proximity extension assay. RESULTS: After correction for false discovery rate, 20 of the 92 inflammatory proteins were significantly decreased in breast tissue after ASA treatment, whereas no systemic effects were detected. In the no-treatment group, protein levels were unaffected. Breast density, measured by LTF on MRI, were unaffected in both groups. ASA significantly decreased the perfusion rate. The perfusion rate correlated positively with local breast tissue concentration of VEGF. CONCLUSIONS: ASA may shape the local breast tissue microenvironment into an anti-tumorigenic state. Trials investigating the effects of low-dose ASA and risk of primary breast cancer among postmenopausal women with maintained high mammographic density are warranted. Trial registration EudraCT: 2017-000317-22.

Cross-vendor multiparametric mapping of the human brain using 3D-QALAS: A multicenter and multivendor study.

PURPOSE: To evaluate a vendor-agnostic multiparametric mapping scheme based on 3D quantification using an interleaved Look-Locker acquisition sequence with a T2 preparation pulse (3D-QALAS) for whole-brain T1, T2, and proton density (PD) mapping. METHODS: This prospective, multi-institutional study was conducted between September 2021 and February 2022 using five different 3T systems from four prominent MRI vendors. The accuracy of this technique was evaluated using a standardized MRI system phantom. Intra-scanner repeatability and inter-vendor reproducibility of T1, T2, and PD values were evaluated in 10 healthy volunteers (6 men; mean age ± SD, 28.0 ± 5.6 y) who underwent scan-rescan sessions on each scanner (total scans = 100). To evaluate the feasibility of 3D-QALAS, nine patients with multiple sclerosis (nine women; mean age ± SD, 48.2 ± 11.5 y) underwent imaging examination on two 3T MRI systems from different manufacturers. RESULTS: Quantitative maps obtained with 3D-QALAS showed high linearity (R2 = 0.998 and 0.998 for T1 and T2, respectively) with respect to reference measurements. The mean intra-scanner coefficients of variation for each scanner and structure ranged from 0.4% to 2.6%. The mean structure-wise test-retest repeatabilities were 1.6%, 1.1%, and 0.7% for T1, T2, and PD, respectively. Overall, high inter-vendor reproducibility was observed for all parameter maps and all structure measurements, including white matter lesions in patients with multiple sclerosis. CONCLUSION: The vendor-agnostic multiparametric mapping technique 3D-QALAS provided reproducible measurements of T1, T2, and PD for human tissues within a typical physiological range using 3T scanners from four different MRI manufacturers.

Liver fibrosis is associated with left ventricular remodeling: insight into the liver-heart axis.

OBJECTIVE: In nonalcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers. METHODS: In this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden. Between November 2017 and July 2018, participants underwent MRI at 1.5 Tesla for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography), left ventricular (LV) structure and function, as well as myocardial native T1 mapping. We analyzed 278 circulating cardiovascular biomarkers using a Bayesian statistical approach. RESULTS: In total, 92 participants were enrolled (mean age 59.5 ± 4.6 years, 32 women). The mean liver stiffness was 2.1 ± 0.4 kPa. 53 participants displayed hepatic steatosis. LV concentricity increased across quartiles of liver stiffness. Neither liver fat nor liver stiffness displayed any relationships to myocardial tissue characteristics (native T1). In a regression analysis, liver stiffness was related to increased LV concentricity. This association was independent of diabetes and liver fat (Beta = 0.26, p = 0.0053), but was attenuated (Beta = 0.17, p = 0.077) when also adjusting for circulating levels of interleukin-1 receptor type 2. CONCLUSION: MRI reveals that liver fibrosis is associated to structural LV remodeling, in terms of increased concentricity, in participants from the general population. This relationship could involve the interleukin-1 signaling. CLINICAL RELEVANCE STATEMENT: Liver fibrosis may be considered a cardiovascular risk factor in patients without cirrhosis. Further research on the mechanisms that link liver fibrosis to left ventricular concentricity may reveal potential therapeutic targets in patients with non-alcoholic fatty liver disease (NAFLD). KEY POINTS: Previously, studies on liver fibrosis and cardiac remodeling have focused on advanced stages of liver fibrosis. Liver fibrosis is associated with left ventricular (LV) concentricity and may relate to interleukin-1 receptor type 2. Interleukin-1 signaling is a potential mechanistic interlink between early liver fibrosis and LV remodeling.

Quantitative Magnetic Resonance Imaging Assessment of the Relationships Between Fat Fraction and R2* Inside Carotid Plaques, and Circulating Lipoproteins.

BACKGROUND: Lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) are morphological features of high-risk atherosclerotic plaques. However, their relationship to circulating lipoproteins is unclear. PURPOSE: To study associations between changes in lipoproteins vs. changes in LRNC (represented by fat fraction [FF]) and IPH (represented by R2*). STUDY TYPE: Prospective. SUBJECTS: Fifty-two patients with carotid plaques, 33 males (63.5%), mean age 72 (±5). FIELD STRENGTH/SEQUENCE: Four-point fast gradient Dixon magnetic resonance imaging (MRI) was used to quantify FF and R2* (to measure IPH) inside plaques and in vessel wall. Turbo-spin echo was used for T1 weighted sequences to guide manual segmentation. ASSESSMENT: Carotid MRI and serum lipid levels were assessed at baseline and at 1-year follow-up. For patients, lipid-lowering therapy was customized to reduce low-density lipoprotein (LDL) levels below 1.8 mmol/L. Segmentation was performed with one set of regions of interest for the plaque and one for the vessel wall at the location of the plaque. Thereby MRI data for FF, R2*, and volumes in plaque- and vessel-wall segmentations could be obtained from baseline and follow-up, as well as changes over the study year. STATISTICAL TESTS: Pearson correlation coefficient for correlations. Paired samples t-test for changes over time. Significance at P < 0.05, 95% confidence interval. RESULTS: LDL decreased significantly (2.19-1.88 mmol/L, Z - 2.9), without correlation to changes in plaque composition, nor to the significant reduction in vessel-wall volume (-106.3 mm3 ). Plaque composition remained unchanged, FF +8.5% (P = 0.366) and R2* +3.5% (P = 0.304). Compared to plaque segmentations, R2* was significantly lower in the vessel-wall segmentations both at baseline (-9.3%) and at follow-up (-9.1%). DATA CONCLUSION: The absence of correlations between changes in lipoproteins and changes in plaque composition indicates more complex relationships between these parameters than previously anticipated. The significant differences in both R2* and volume dynamics comparing plaque segmentations and vessel-wall segmentations suggest differences in their pathobiology of atherosclerosis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Validation of Rapid Magnetic Resonance Myelin Imaging in Multiple Sclerosis.

OBJECTIVE: Magnetic resonance imaging (MRI) is essential for multiple sclerosis diagnostics but is conventionally not specific to demyelination. Myelin imaging is often hampered by long scanning times, complex postprocessing, or lack of clinical approval. This study aimed to assess the specificity, robustness, and clinical value of Rapid Estimation of Myelin for Diagnostic Imaging, a new myelin imaging technique based on time-efficient simultaneous T1 /T2 relaxometry and proton density mapping in multiple sclerosis. METHODS: Rapid myelin imaging was applied using 3T MRI ex vivo in 3 multiple sclerosis brain samples and in vivo in a prospective cohort of 71 multiple sclerosis patients and 21 age/sex-matched healthy controls, with scan-rescan repeatability in a subcohort. Disability in patients was assessed by the Expanded Disability Status Scale and the Symbol Digit Modalities Test at baseline and 2-year follow-up. RESULTS: Rapid myelin imaging correlated with myelin-related stains (proteolipid protein immunostaining and Luxol fast blue) and demonstrated good precision. Multiple sclerosis patients had, relative to controls, lower normalized whole-brain and normal-appearing white matter myelin fractions, which correlated with baseline cognitive and physical disability. Longitudinally, these myelin fractions correlated with follow-up physical disability, even with correction for baseline disability. INTERPRETATION: Rapid Estimation of Myelin for Diagnostic Imaging provides robust myelin quantification that detects diffuse demyelination in normal-appearing tissue in multiple sclerosis, which is associated with both cognitive and clinical disability. Because the technique is fast, with automatic postprocessing and US Food and Drug Administration/CE clinical approval, it can be a clinically feasible biomarker that may be suitable to monitor myelin dynamics and evaluate treatments aiming at remyelination. ANN NEUROL 2020;87:710-724.

Towards Automated Quantification of Vessel Wall Composition Using MRI.

BACKGROUND: MRI can be used to generate fat fraction (FF) and R2* data, which have been previously shown to characterize the plaque compositional features lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in the carotid arteries (CAs). Previously, these data were extracted from CA plaques using time-consuming manual analyses. PURPOSE: To design and demonstrate a method for segmenting the CA and extracting data describing the composition of the vessel wall. STUDY TYPE: Prospective. SUBJECTS: 31 subjects from the Swedish CArdioPulmonary bioImage Study (SCAPIS). FIELD STRENGTH/SEQUENCES: T1 -weighted (T1 W) quadruple inversion recovery, contrast-enhanced MR angiography (CE-MRA), and 4-point Dixon data were acquired at 3T. ASSESSMENT: The vessel lumen of the CA was automatically segmented using support vector machines (SVM) with CE-MRA data, and the vessel wall region was subsequently delineated. Automatically generated segmentations were quantitatively measured and three observers visually compared the segmentations to manual segmentations performed on T1 w images. Dixon data were used to generate FF and R2* maps. Both manually and automatically generated segmentations of the CA and vessel wall were used to extract compositional data. STATISTICAL TESTS: Two-tailed t-tests were used to examine differences between results generated using manual and automated analyses, and among different configurations of the automated method. Interobserver agreement was assessed with Fleiss' kappa. RESULTS: Automated segmentation of the CA using SVM had a Dice score of 0.89 ± 0.02 and true-positive ratio 0.93 ± 0.03 when compared against ground truth, and median qualitative score of 4/5 when assessed visually by multiple observers. Vessel wall regions of 0.5 and 1 mm yielded compositional information similar to that gained from manual analyses. Using the 0.5 mm vessel wall region, the mean difference was 0.1 ± 2.5% considering FF and 1.1 ± 5.7[1/s] for R2*. LEVEL OF EVIDENCE: 1. TECHNICAL EFFICACY STAGE: 1. J. Magn. Reson. Imaging 2020;52:710-719.

3D quantitative synthetic MRI-derived cortical thickness and subcortical brain volumes: Scan-rescan repeatability and comparison with conventional T1 -weighted images.

BACKGROUND: Previous quantitative synthetic MRI of the brain has been solely performed in 2D. PURPOSE: To evaluate the feasibility of the recently developed sequence 3D-QALAS for brain cortical thickness and volumetric analysis. STUDY TYPE: Reproducibility/repeatability study. SUBJECTS: Twenty-one healthy volunteers (35.6 ± 13.8 years). FIELD STRENGTH/SEQUENCE: 3D T1 -weighted fast spoiled gradient recalled echo (FSPGR) sequence was performed once, and 3D-QALAS sequence was performed twice with a 3T scanner. ASSESSMENT: FreeSurfer and FIRST were used to measure cortical thickness and volume of subcortical structures, respectively. Agreement with FSPGR and scan-rescan repeatability were evaluated for 3D-QALAS. STATISTICAL TESTS: Percent relative difference and intraclass correlation coefficient (ICC) were used to assess reproducibility and scan-rescan repeatability of the 3D-QALAS sequence-derived measurements. RESULTS: Percent relative difference compared with FSPGR in cortical thickness of the whole cortex was 3.1%, and 89% of the regional areas showed less than 10% relative difference in cortical thickness. The mean ICC across all regions was 0.65, and 74% of the structures showed substantial to almost perfect agreement. For volumes of subcortical structures, the median percent relative differences were lower than 10% across all subcortical structures, except for the accumbens area, and all structures showed ICCs of substantial to almost perfect agreement. For the scan-rescan test, percent relative difference in cortical thickness of the whole cortex was 2.3%, and 97% of the regional areas showed less than 10% relative difference in cortical thickness. The mean ICC across all regions was 0.73, and 80% showed substantial to almost perfect agreement. For volumes of subcortical structures, relative differences were less than 10% across all subcortical structures except for the accumbens area, and all structures showed ICCs of substantial to almost perfect agreement. DATA CONCLUSION: 3D-QALAS could be reliably used for measuring cortical thickness and subcortical volumes in most brain regions. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1834-1842.

Longitudinal changes in myocardial T1 and T2 relaxation times related to diffuse myocardial fibrosis in aortic stenosis; before and after aortic valve replacement.

BACKGROUND: Diffuse myocardial fibrosis is associated with adverse outcomes, although detection and quantification is challenging. Cardiac MR relaxation times mapping represents a promising imaging biomarker for diffuse myocardial fibrosis. PURPOSE: To investigate whether relaxation times can detect longitudinal changes in myocardial tissue composition associated with diffuse fibrosis in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). STUDY TYPE: Prospective longitudinal study. POPULATION/SUBJECTS/PHANTOM/SPECIMEN/ANIMAL MODEL: Fifteen patients with severe AS. FIELD STRENGTH/SEQUENCE: 3T / 3(3)3(3)5-MOLLI, T2 -GraSE, and 3D-QALAS. ASSESSMENT: Patients underwent MR examinations at three timepoints: before AVR, as well as 3 and 12 months after AVR. Data from each patient was analyzed in 16 myocardial segments. STATISTICAL TESTS: The segment-wise T1 and T2 data were analyzed over time after surgery using linear mixed models for repeated measures analysis. RESULTS: The results showed that T1 relaxation times were significantly (P < 0.05) shorter 3 and 12 months postoperative than preoperative and that the T2 relaxation times were significantly (P < 0.05) longer 3 and 12 months postoperative than preoperative for both 3D and 2D mapping methods. No significant changes were seen between 3 and 12 months postoperative for any of the methods (P = 0.06/0.19 for T1 with 3D-QALAS/MOLLI and P = 0.09/0.25 for T2 with 3D-QALAS/GraSE). DATA CONCLUSION: We demonstrated that changes in myocardial relaxation times and thus tissue characteristics can be observed within 3 months after AVR surgery. The significant changes in relaxation times from preoperative examinations to the follow-up may be interpreted as a reduction of interstitial fibrosis in the left ventricular wall. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018.

Temperature-corrected postmortem 3-T MR quantification of histopathological early acute and chronic myocardial infarction: a feasibility study.

The goal of the present study was to evaluate if quantitative postmortem cardiac 3-T magnetic resonance (QPMCMR) T1 and T2 relaxation times and proton density values of histopathological early acute and chronic myocardial infarction differ to the quantitative values of non-pathologic myocardium and other histopathological age stages of myocardial infarction with regard to varying corpse temperatures. In 60 forensic corpses (25 female, 35 male), a cardiac 3-T MR quantification sequence was performed prior to autopsy and cardiac dissection. Core body temperature was assessed during MR examinations. Focal myocardial signal alterations in synthetically generated MR images were measured for their T1, T2, and proton density (PD) values. Locations of signal alteration measurements in PMCMR were targeted at heart dissection, and myocardial tissue specimens were taken for histologic examinations. Quantified signal alterations in QPMCMR were correlated to their according histologic age stage of myocardial infarction, and quantitative values were corrected for a temperature of 37 °C. In QPMCMR, 49 myocardial signal alterations were detected in 43 of 60 investigated hearts. Signal alterations were diagnosed histologically as early acute (n = 16), acute (n = 10), acute with hemorrhagic component (n = 9), subacute (n = 3), and chronic (n = 11) myocardial infarction. Statistical analysis revealed that based on their temperature-corrected quantitative T1, T2, and PD values, a significant difference between early acute, acute, and chronic myocardial infarction can be determined. It can be concluded that quantitative 3-T postmortem cardiac MR based on temperature-corrected T1, T2, and PD values may be feasible for pre-autopsy diagnosis of histopathological early acute, acute, and chronic myocardial infarction, which needs to be confirmed histologically.

Quantitative fat and R2* mapping in vivo to measure lipid-rich necrotic core and intraplaque hemorrhage in carotid atherosclerosis.

PURPOSE: The aim of this work was to quantify the extent of lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) in atherosclerotic plaques. METHODS: Patients scheduled for carotid endarterectomy underwent four-point Dixon and T1-weighted magnetic resonance imaging (MRI) at 3 Tesla. Fat and R2* maps were generated from the Dixon sequence at the acquired spatial resolution of 0.60 × 0.60 × 0.70 mm voxel size. MRI and three-dimensional (3D) histology volumes of plaques were registered. The registration matrix was applied to segmentations denoting LRNC and IPH in 3D histology to split plaque volumes in regions with and without LRNC and IPH. RESULTS: Five patients were included. Regarding volumes of LRNC identified by 3D histology, the average fat fraction by MRI was significantly higher inside LRNC than outside: 12.64 ± 0.2737% versus 9.294 ± 0.1762% (mean ± standard error of the mean [SEM]; P < 0.001). The same was true for IPH identified by 3D histology, R2* inside versus outside IPH was: 71.81 ± 1.276 s-1 versus 56.94 ± 0.9095 s-1 (mean ± SEM; P < 0.001). There was a strong correlation between the cumulative fat and the volume of LRNC from 3D histology (R2 = 0.92) as well as between cumulative R2* and IPH (R2 = 0.94). CONCLUSION: Quantitative mapping of fat and R2* from Dixon MRI reliably quantifies the extent of LRNC and IPH. Magn Reson Med 78:285-296, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Temperature-corrected post-mortem 1.5 T MRI quantification of non-pathologic upper abdominal organs.

OBJECTIVES: The present study aimed to evaluate if simultaneous temperature-corrected T1, T2, and proton density (PD) 1.5 T post-mortem MR quantification [quantitative post-mortem magnetic resonance imaging (QPMMRI)] is feasible for characterizing and discerning non-pathologic upper abdominal organs (liver, spleen, pancreas, kidney) with regard to varying body temperatures. METHODS: QPMMRI was performed on 80 corpses (25 females, 55 males; mean age 56.2 years, SD 17.2) prior to autopsy. Core body temperature was measured during QPMMRI. Quantitative T1, T2, and PD values were measured in the liver, pancreas, spleen, and left kidney and temperature corrected to 37 °C. Histologic examinations were conducted on each measured organ to determine non-pathologic organs. Quantitative T1, T2, and PD values of non-pathologic organs were ANOVA tested against values of other non-pathologic organ types. RESULTS: Based on temperature-corrected quantitative T1, T2, and PD values, ANOVA testing verified significant differences between the non-pathologic liver, spleen, pancreas, and left kidneys. CONCLUSIONS: Temperature-corrected 1.5 T QPMMRI based on T1, T2, and PD values may be feasible for characterization and differentiation of the non-pathologic liver, spleen, pancreas, and kidney. The results may provide a base for future specific pathology diagnosis of upper abdominal organs in post-mortem imaging.

Post-mortem 1.5T MR quantification of regular anatomical brain structures.

Recently, post-mortem MR quantification has been introduced to the field of post-mortem magnetic resonance imaging. By usage of a particular MR quantification sequence, T1 and T2 relaxation times and proton density (PD) of tissues and organs can be quantified simultaneously. The aim of the present basic research study was to assess the quantitative T1, T2, and PD values of regular anatomical brain structures for a 1.5T application and to correlate the assessed values with corpse temperatures. In a prospective study, 30 forensic cases were MR-scanned with a quantification sequence prior to autopsy. Body temperature was assessed during MR scans. In synthetically calculated T1, T2, and PD-weighted images, quantitative T1, T2 (both in ms) and PD (in %) values of anatomical structures of cerebrum (Group 1: frontal gray matter, frontal white matter, thalamus, internal capsule, caudate nucleus, putamen, and globus pallidus) and brainstem/cerebellum (Group 2: cerebral crus, substantia nigra, red nucleus, pons, cerebellar hemisphere, and superior cerebellar peduncle) were assessed. The investigated brain structures of cerebrum and brainstem/cerebellum could be characterized and differentiated based on a combination of their quantitative T1, T2, and PD values. MANOVA testing verified significant differences between the investigated anatomical brain structures among each other in Group 1 and Group 2 based on their quantitative values. Temperature dependence was observed mainly for T1 values, which were slightly increasing with rising temperature in the investigated brain structures in both groups. The results provide a base for future computer-aided diagnosis of brain pathologies and lesions in post-mortem magnetic resonance imaging.

Temperature dependence of postmortem MR quantification for soft tissue discrimination.

OBJECTIVES: To investigate and correct the temperature dependence of postmortem MR quantification used for soft tissue characterization and differentiation in thoraco-abdominal organs. MATERIAL AND METHODS: Thirty-five postmortem short axis cardiac 3-T MR examinations were quantified using a quantification sequence. Liver, spleen, left ventricular myocardium, pectoralis muscle and subcutaneous fat were analysed in cardiac short axis images to obtain mean T1, T2 and PD tissue values. The core body temperature was measured using a rectally inserted thermometer. The tissue-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. RESULTS: In a 3D plot comprising the combined data of T1, T2 and PD, different organs/tissues could be well differentiated from each other. The quantitative values were influenced by the temperature. T1 in particular exhibited strong temperature dependence. The correction of quantitative values to a temperature of 37 °C resulted in better tissue discrimination. CONCLUSION: Postmortem MR quantification is feasible for soft tissue discrimination and characterization of thoraco-abdominal organs. This provides a base for computer-aided diagnosis and detection of tissue lesions. The temperature dependence of the T1 values challenges postmortem MR quantification. Equations to correct for the temperature dependence are provided. KEY POINTS: • Postmortem MR quantification is feasible for soft tissue discrimination and characterization • Temperature dependence of the T1 values challenges the MR quantification approach • The results provide the basis for computer-aided postmortem MRI diagnosis • Diagnostic criteria may also be applied for living patients.

Postmortem MR quantification of the heart for characterization and differentiation of ischaemic myocardial lesions.

OBJECTIVES: Recently, an MRI quantification sequence has been developed which can be used to acquire T1- and T2-relaxation times as well as proton density (PD) values. Those three quantitative values can be used to describe soft tissue in an objective manner. The purpose of this study was to investigate the applicability of quantitative cardiac MRI for characterization and differentiation of ischaemic myocardial lesions of different age. MATERIALS AND METHODS: Fifty post-mortem short axis cardiac 3 T MR examinations have been quantified using a quantification sequence. Myocardial lesions were identified according to histology and appearance in MRI images. Ischaemic lesions were assessed for mean T1-, T2- and proton density values. Quantitative values were plotted in a 3D-coordinate system to investigate the clustering of ischaemic myocardial lesions. RESULTS: A total of 16 myocardial lesions detected in MRI images were histologically characterized as acute lesions (n = 8) with perifocal oedema (n = 8), subacute lesions (n = 6) and chronic lesions (n = 2). In a 3D plot comprising the combined quantitative values of T1, T2 and PD, the clusters of all investigated lesions could be well differentiated from each other. CONCLUSION: Post-mortem quantitative cardiac MRI is feasible for characterization and discrimination of different age stages of myocardial infarction. KEY POINTS: • MR quantification is feasible for characterization of different stages of myocardial infarction. • The results provide the base for computer-aided MRI cardiac infarction diagnosis. • Diagnostic criteria may also be applied for living patients.

Postmortem quantitative 1.5-T MRI for the differentiation and characterization of serous fluids, blood, CSF, and putrefied CSF.

The purpose of the present study was to investigate whether serous fluids, blood, cerebrospinal fluid (CSF), and putrefied CSF can be characterized and differentiated in synthetically calculated magnetic resonance (MR) images based on their quantitative T1, T2, and proton density (PD) values. Images from 55 postmortem short axis cardiac and 31 axial brain 1.5-T MR examinations were quantified using a quantification sequence. Serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF were analyzed for their mean T1, T2, and PD values. Body core temperature was measured during the MRI scans. The fluid-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. In a 3D plot as well as in statistical analysis, the quantitative T1, T2 and PD values of serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF could be well differentiated from each other. The quantitative T1 and T2 values were temperature-dependent. Correction of quantitative values to a temperature of 37 °C resulted in significantly better discrimination between all investigated fluid mediums. We conclude that postmortem 1.5-T MR quantification is feasible to discriminate between blood, serous fluids, CSF, and putrefied CSF. This finding provides a basis for the computer-aided diagnosis and detection of fluids and hemorrhages.

Simultaneous three-dimensional myocardial T1 and T2 mapping in one breath hold with 3D-QALAS.

BACKGROUND: Quantification of the longitudinal- and transverse relaxation time in the myocardium has shown to provide important information in cardiac diagnostics. Methods for cardiac relaxation time mapping generally demand a long breath hold to measure either T1 or T2 in a single 2D slice. In this paper we present and evaluate a novel method for 3D interleaved T1 and T2 mapping of the whole left ventricular myocardium within a single breath hold of 15 heartbeats. METHODS: The 3D-QALAS (3D-quantification using an interleaved Look-Locker acquisition sequence with T2 preparation pulse) is based on a 3D spoiled Turbo Field Echo sequence using inversion recovery with interleaved T2 preparation. Quantification of both T1 and T2 in a volume of 13 slices with a resolution of 2.0x2.0x6.0 mm is obtained from five measurements by using simulations of the longitudinal magnetizations Mz. This acquisition scheme is repeated three times to sample k-space. The method was evaluated both in-vitro (validated against Inversion Recovery and Multi Echo) and in-vivo (validated against MOLLI and Dual Echo). RESULTS: In-vitro, a strong relation was found between 3D-QALAS and Inversion Recovery (R = 0.998; N = 10; p < 0.01) and between 3D-QALAS and Multi Echo (R = 0.996; N = 10; p < 0.01). The 3D-QALAS method showed no dependence on e.g. heart rate in the interval of 40-120 bpm. In healthy myocardium, the mean T1 value was 1083 ± 43 ms (mean ± SD) for 3D-QALAS and 1089 ± 54 ms for MOLLI, while the mean T2 value was 50.4 ± 3.6 ms 3D-QALAS and 50.3 ± 3.5 ms for Dual Echo. No significant difference in in-vivo relaxation times was found between 3D-QALAS and MOLLI (N = 10; p = 0.65) respectively 3D-QALAS and Dual Echo (N = 10; p = 0.925) for the ten healthy volunteers. CONCLUSIONS: The 3D-QALAS method has demonstrated good accuracy and intra-scan variability both in-vitro and in-vivo. It allows rapid acquisition and provides quantitative information of both T1 and T2 relaxation times in the same scan with full coverage of the left ventricle, enabling clinical application in a broader spectrum of cardiac disorders.

Magnetic resonance imaging goes postmortem: noninvasive detection and assessment of myocardial infarction by postmortem MRI.

OBJECTIVE: To investigate the performance of postmortem magnetic resonance imaging (pmMRI) in identification and characterization of lethal myocardial infarction in a non-invasive manner on human corpses. MATERIALS AND METHODS: Before forensic autopsy, 20 human forensic corpses were examined on a 1.5-T system for the presence of myocardial infarction. Short axis, transversal and longitudinal long axis images (T1-weighted; T2-weighted; PD-weighted) were acquired in situ. In subsequent autopsy, the section technique was adapted to short axis images. Histological investigations were conducted to confirm autopsy and/or radiological diagnoses. RESULTS: Nineteen myocardial lesions were detected and age staged with pmMRI, of which 13 were histologically confirmed (chronic, subacute and acute). Six lesions interpreted as peracute by pmMRI showed no macroscopic or histological finding. Five of the six peracute lesions correlated well to coronary pathology, and one case displayed a severe hypertrophic alteration. CONCLUSION: pmMRI reliably demonstrates chronic, subacute and acute myocardial infarction in situ. In peracute cases pmMRI may display ischemic lesions undetectable at autopsy and routine histology. pmMRI has the potential to substantiate autopsy and to counteract the loss of reliable information on causes of death due to the recent disappearance of the clinical autopsy.

18Fluorodeoxyglucose uptake in relation to fat fraction and R2* in atherosclerotic plaques, using PET/MRI: a pilot study.

Inflammation inside Atherosclerotic plaques represents a major pathophysiological process driving plaques towards rupture. Pre-clinical studies suggest a relationship between lipid rich necrotic core, intraplaque hemorrhage and inflammation, not previously explored in patients. Therefore, we designed a pilot study to investigate the feasibility of assessing the relationship between these plaque features in a quantitative manner using PET/MRI. In 12 patients with high-grade carotid stenosis the extent of lipid rich necrotic core and intraplaque hemorrhage was quantified from fat and R2* maps acquired with a previously validated 4-point Dixon MRI sequence in a stand-alone MRI. PET/MRI was used to measure 18F-FDG uptake. T1-weighted images from both scanners were used for registration of the quantitative Dixon data with the PET images. The plaques were heterogenous with respect to their volumes and composition. The mean values for the group were as follows: fat fraction (FF) 0.17% (± 0.07), R2* 47.6 s-1 (± 10.9) and target-to-blood pool ratio (TBR) 1.49 (± 0.48). At group level the correlation between TBR and FFmean was - 0.406, p 0.19 and for TBR and R2*mean 0.259, p 0.42. The lack of correlation persisted when analysed on a patient-by-patient basis but the study was not powered to draw definitive conclusions. We show the feasibility of analysing the quantitative relationship between lipid rich necrotic cores, intraplaque haemorrhage and plaque inflammation. The 18F-FDG uptake for most patients was low. This may reflect the biological complexity of the plaques and technical aspects inherent to 18F-FDG measurements.Trial registration: ISRCTN, ISRCTN30673005. Registered 05 January 2021, retrospectively registered.

Rapid T1 quantification based on 3D phase sensitive inversion recovery.

BACKGROUND: In Contrast Enhanced Magnetic Resonance Imaging fibrotic myocardium can be distinguished from healthy tissue using the difference in the longitudinal T1 relaxation after administration of Gadolinium, the so-called Late Gd Enhancement. The purpose of this work was to measure the myocardial absolute T1 post-Gd from a single breath-hold 3D Phase Sensitivity Inversion Recovery sequence (PSIR). Equations were derived to take the acquisition and saturation effects on the magnetization into account. METHODS: The accuracy of the method was investigated on phantoms and using simulations. The method was applied to a group of patients with suspected myocardial infarction where the absolute difference in relaxation of healthy and fibrotic myocardium was measured at about 15 minutes post-contrast. The evolution of the absolute R1 relaxation rate (1/T1) over time after contrast injection was followed for one patient and compared to T1 mapping using Look-Locker. Based on the T1 maps synthetic LGE images were reconstructed and compared to the conventional LGE images. RESULTS: The fitting algorithm is robust against variation in acquisition flip angle, the inversion delay time and cardiac arrhythmia. The observed relaxation rate of the myocardium is 1.2 s-1, increasing to 6 - 7 s-1 after contrast injection and decreasing to 2 - 2.5 s-1 for healthy myocardium and to 3.5 - 4 s-1 for fibrotic myocardium. Synthesized images based on the T1 maps correspond very well to actual LGE images. CONCLUSIONS: The method provides a robust quantification of post-Gd T1 relaxation for a complete cardiac volume within a single breath-hold.

Machine Learning and Multiparametric Brain MRI to Differentiate Hereditary Diffuse Leukodystrophy with Spheroids from Multiple Sclerosis.

BACKGROUND AND PURPOSE: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) and multiple sclerosis (MS) are demyelinating and neurodegenerative disorders that can be hard to distinguish clinically and radiologically. HDLS is a rare disorder compared to MS, which has led to occurrent misdiagnosis of HDLS as MS. That is problematic since their prognosis and treatment differ. Both disorders are investigated by MRI, which could help to identify patients with high probability of having HDLS, which could guide targeted genetic testing to confirm the HDLS diagnosis. METHODS: Here, we present a machine learning method based on quantitative MRI that can achieve a robust classification of HDLS versus MS. Four HDLS and 14 age-matched MS patients underwent a quantitative brain MRI protocol (synthetic MRI) at 3 Tesla (T) (scan time <7 minutes). We also performed a repeatability analysis of the predicting features to assess their generalizability by scanning a healthy control with five scan-rescans at 3T and 1.5T. RESULTS: Our predicting features were measured with an average confidence interval of 1.7% (P = .01), at 3T and 2.3% (P = .01) at 1.5T. The model gave a 100% correct classification of the cross-validation data when using 5-11 predicting features. When the maximum measurement noise was inserted in the model, the true positive rate of HDLS was 97.2%, while the true positive rate of MS was 99.6%. CONCLUSIONS: This study suggests that computer-assistance in combination with quantitative MRI may be helpful in aiding the challenging differential diagnosis of HDLS versus MS.