Journal of Magnetic Resonance Imaging

Background & AimsFor a range of liver malignancies, the only curative treatment option may be hepatectomy, which may have fatal complications. Therefore, an unbiased pre-operative risk assessment is vital, however, at present the assessment is typically based on global liver function only. Magnetic resonance imaging (MRI) modalities have the possibility to aid this assessment, by introducing additional characterization of liver parenchymal, such as non-invasive quantification of steatosis, fibrosis, and uptake function, both for global and regional assessment. To this cause, we here present a prospective observation study (LIFE), in which patients underwent extensive MR-examinations both before and after resective-surgery. Approach and ResultsA total of 13 patients undergoing hepatectomy underwent a pre- (n=13) and post (m=5) multimodal MRI examination (within 3-5 days of the surgery) (Fig. 1B). The multimodal MR-examination included DCE, 3D-MRE, fat fraction measurements (PDFF by MRS, 6PD). Using these measurements, we also construct individual patient profiles by including conventional functional, and volumetric measurements, into a multi-parametric space. As a proof of concept, the areas of each profile, denoted multiparametric profile area (MPA, and aMPA) were calculated, to create a measurement comprising information from all modalities. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/24302306v1_fig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1ce4181org.highwire.dtl.DTLVardef@2eb05eorg.highwire.dtl.DTLVardef@13d1057org.highwire.dtl.DTLVardef@1fbf9d5_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Study-design and the multi-modal magnetic resonance imaging (MRI) examination. (A) Multi-modal MR-protocol and conventional function test. The examination can be divided into five segments. The first segment (dark green box) was the elastography (MRE) at 33 Hz vibration frequency, measuring tissue stiffness. The second segment (teal) was dynamic contrast enhanced (DCE) MRI using the hepatocyte specific contrast agent gadoxetic acid (Gd-EOB-DTPA, Primovist, Bayer Schering Pharma, Berlin, Germany). The third box (light green) was quantitative MRI. Fat fraction via both spectroscopy (MRS) and 6-Point Dixon imaging (6PD). Also, the liver iron content (LIC) was estimated using the relaxation rate R2* obtained via standard T2-weighted imaging. We also performed laboratory function tests including galactose breath test (GBT), Indocyanine Green retention rate (R15) and disappearance rate (PDR), as well as measured bilirubin and albumin. (B) Study setup. A total of 13 patients, all undergoing hepatectomy, underwent a multi-modal MRI examination 3-5 days before and after surgery. A total of five patients were able and willing to undergo the post-surgery MRI examination. C_FIG At a group-level, no clear pattern emerged of MPA or aMPA between groups with different extent of resection. In contrast, on a case-by-case basis, several parameters contributed to high individual MPA or aMPA-values, suggesting tissue abnormalities. With respect to regional DCE measurements, i.e., relative enhancement at 20 minutes, a clear variation between function in segments, within and between the individuals, was observed. ConclusionsIn this combined pre- and post-observational case-based study ranging from very extensive (i) liver surgery to minor (ii), or none (iii), we aimed to describe how a multi-modal MRI examination before hepatectomy could yield valuable information for the pre-operative assessment, with a particular focus on a Couinaud-segmental level. The use of a multi-modal approach allows for a broad spectral characterization of several aspects of the remnant tissue. However, the effectiveness and clinical benefit of each parameter, and how to further optimize an abbreviated clinical MR-protocol needs to be confirmed.

Despite the increased water content in fibrotic livers, numerous studies reported a decrease in ADC (apparent diffusion coefficient) in liver fibrosis. We argue that the ADC decrease in fibrotic livers is due to the T2 shine-through of ADC, as the longer T2 in liver fibrosis leads to less signal decay between the low and high b-value images. The metric slow diffusion coefficient (SDC) was proposed to mitigate the difficulties associated with this T2 shine-through of ADC. This study calculated ADC and SDC of one rat study with liver fibrosis induced by biliary duct ligation (BDL), and three sets of human liver fibrosis data. To tease out the menopausal effect on SDC, only the results of mens livers were analysed for the human datasets. The rat study showed, liver ADC decreased stepwise (in weeks after BDL procedure) following fibrosis induction, SDC increased stepwise. In human studies, all three datasets consistently showed advanced fibrosis had an ADC lower than that of earlier stage fibrosis; advanced fibrosis had a SDC higher than that of earlier stage fibrosis. When each liver SDC datum was normalized by the mean value of the controls without fibrosis, and the three human datasets were summed together, stage-1 liver fibrosis had a normalized SDC value lower than that of the controls, and there was a stepwise increase of SDC value from stage-1 liver fibrosis to stage-4 liver fibrosis. It is known that liver fibrosis is associated with lower perfusion, higher iron/susceptibility, and higher water content, and these three factors all contribute to the lower ADC measure. Higher iron/susceptibility lowers SDC measure, whereas higher water content elevates SDC measure. It is likely that for early-stage fibrosis, the net effect of susceptibility and water leads to a lower SDC, while for advanced fibrosis, the net effect leads to a higher SDC.

AimLiver vessel density can be evaluated by an imaging biomarker DDVD (diffusion derived vessel density): DDVD/area(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 (s/mm2); ROIarea0 and ROIarea2 refer to the region-of-interest on b= 0 or 2 images; and Sb2 may be replaced by Sb15 (b=15). This concept was validated in this study.\n\nMaterials and MethodsLiver diffusion images were acquired at 1.5T. For a scan-rescan repeatability study of 6 subjects, b-values of 0 and 2 were used. The validation study composed of 26 healthy volunteers and 19 consecutive suspected chronic viral hepatitis-b patients, and diffusion images with 16 b-values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, 600 were acquired. Four patients did not have liver fibrosis, and the rest were four stage-1, three stage-2, four stage 3, and one stage-4 patients respectively.\n\nResultsIntraclass correlation coefficient for repeatability was 0.994 for DDVD/area(Sb0Sb2), and 0.978 for DDVD/area(Sb0Sb15). In the validation study, DDVD/area(Sb0Sb2) and area(Sb0Sb15) were 14.80{+/-}3.06 and 26.58{+/-}3.97 for healthy volunteers, 10.51{+/-}1.51 and 20.15{+/-}2.21 for stage 1-2 fibrosis patients, and 9.42{+/-}0.87 and 19.42{+/-}1.89 for stage 3-4 fibrosis patients. For 16 patients where IVIM analysis was performed, a combination of DDVD/area, PF, and Dfast achieved the best differentiation for non-fibrotic livers and fibrotic livers. DDVD/area were weakly correlated with PF or Dfast.\n\nConclusionBoth DDVD/area(Sb0Sb2) and area(Sb0Sb15) are useful imaging biomarker to separate fibrotic and non-fibrotic livers, with fibrotic livers had lower measurements.

Background: Recently, a posterior pathway for fluid drainage from the retina to the meningeal lymphatics in the optic nerve (ON) sheath was identified in rodents using intravitreal imaging tracers directly injected into the ocular-globe. Fluid and solute clearance along this pathway may be associated with many diseases. However, intravitreal tracers are rarely used in clinical imaging. As intravenous Gadolinium-based-contrast-agent (GBCA) can enter the globe via the blood-ocular-barriers, it may provide an alternative approach to image this pathway. Purpose: To establish a clinically feasible intravenous GBCA-based MRI approach for tracking fluid and solute transport along the posterior lymphatic pathway in the ocular glymphatic system. Materials & Methods: This prospective study was conducted from March 2021 to September 2022 in healthy participants. Dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was performed before, immediately and 4 hours after intravenous-GBCA administration to track GBCA distribution in aqueous humor (AH) and cerebrospinal fluid (CSF) in regions-of-interest (ROIs) in the globe (anterior-cavity, vitreous-body), in the intraorbital and extraorbital ON, and in the intracranial CSF space proximal to the ON (chiasmatic-cistern, interpeduncular-cistern). Kruskal-Wallis tests with post-hoc Dunn's tests were used for group comparisons. Results: Sixteen healthy participants (mean age +/- SD: 51 +/- 21 years, 5 men) were recruited. Intravenous-GBCA enhancement was observed in all ROIs immediately after injection. At 4-hour-post-GBCA, the vitreous body showed a trend of smaller enhancement area (55 +/- 11% versus 49 +/- 11%, P=.14) and lower GBCA-concentration (0.044 +/- 0.014 versus 0.028 +/- 0.010 mmol/L, P=.07) compared to immediate-post-GBCA. The intraorbital ON showed more widespread enhancement (39 +/- 5% versus 59 +/- 6%, P=.01) and significantly higher GBCA-concentration (0.023 +/- 0.009 versus 0.059 +/- 0.015 mmol/L, P<.001) at 4-hour-post-GBCA. Conclusion: Dynamic fluid and solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy participants was measured by tracking intravenous-GBCAs entering the globe via the blood-ocular-barriers using cDSC-MRI.

Introduction The superior longitudinal fasciculus (SLF) is a major association fiber bundle implicated in cognition, visuospatial attention, language, and motor control, and its impairment is linked to several neurological and neuropsychiatric disorders. This proof-of-concept study was performed with three main objectives in healthy adults. First, to fuse whole brain spectroscopic (WBSI) and diffusion MRI (dMRI) derived parametric maps along the SLF I and II segments to quantify their spatial concordance, second, to evaluate regional metabolite concentrations and microstructural properties along these trajectories and finally, to determine the relationships between the WBSI and dMRI parameters within these segments. Methods Ten healthy adults (4F, 6M; mean age 31.4 {+/-} 7.53 years) underwent 3T MRI including multi-shell high angular resolution diffusion imaging and WBSI. After preprocessing and non-linear co-registration, WBSI-derived white matter metabolite maps and neurite orientation dispersion and density imaging (NODDI) / diffusion tensor imaging (DTI) derived parametric maps were spatially aligned and projected along the centroid of reconstructed SLF I and II segments divided into 20 discrete, anatomically contiguous sections. Results A strong spatial alignment between WBSI and dMRI imaging modalities was confirmed by mutual information and Pearson's correlation analyses. Intra-subject repeatability, as assessed from a single participant scanned three times, demonstrated high tract reconstruction reliability (mean Dice similarity coefficients >0.79; track density-weighted Dice >0.97) and acceptable intra-subject coefficients of variation. Inter-subject coefficients of variation were within acceptable ranges ({approx}3-17%) for most parameters, with free water fraction (fiso) exhibiting relatively higher variability. Single and multivariate regression analyses revealed significant associations between WBSI and dMRI tract profiles: choline/creatine (Cho/Cr) and choline/ N-acetyl aspartate (Cho/NAA) ratios showed positive linear associations with intra-cellular volume fraction (ficvf) and fractional anisotropy (FA), and negative associations with mean diffusivity (MD) along bilateral SLF I, with ficvf and MD identified as the strongest combined predictors of metabolite ratios. Conclusion Co-localization/fusion of WBSI and NODDI/DTI data into one framework offers a reliable, user-independent way for mapping regional metabolite and microstructural alterations along the path of SLF. Moving forward, this image processing pipeline has the potential to enhance diagnosis and clinical assessment of neurological disorders linked to SLF damage.

Thanks to the rapid evolution of therapeutic strategies for muscular and neuromuscular diseases, the identification of quantitative biomarkers for disease identification and monitoring has become crucial. Magnetic resonance imaging (MRI) has been playing an important role by noninvasively assessing structural and functional muscular changes. This exploratory study investigated the potential of dynamic MRI during neuromuscular electrical stimulation (NMES) to detect differences between healthy controls (HCs) and patients with metabolic and myotonic myopathies. The study included 14 HCs and 10 patients with confirmed muscular diseases. All individuals were scanned with 3T MRI with a protocol that included a multi-echo gradient echo sequence for fat fraction quantification, multi-echo spin-echo for water T2 relaxation time calculation, and 3D phase contrast sequences during NMES. The strain tensor, buildup and release rates were calculated from velocity datasets. Results showed that strain and strain buildup rate were reduced in the soleus muscle of patients compared to HCs, suggesting these parameters could serve as biomarkers of muscle dysfunction. Notably, there were no significant differences in fat fraction or water T2 measurements between patients and HCs, indicating that the observed changes reflect alterations in muscle contractile properties that are not reflected by structural changes. The findings provide preliminary evidence that dynamic muscle MRI during NMES can detect abnormalities in muscle contraction in patients with myotonia and metabolic myopathies, warranting further research with larger, more homogeneous patient cohorts.

BackgroundAccurate differentiation of benign and malignant focal liver lesions (FLLs) is essential for clinical decision-making. Magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) are advanced MRI techniques used for noninvasive lesion characterization, but their comparative diagnostic performance has not been definitively established. ObjectiveTo systematically compare the diagnostic accuracy of MRE and DWI for distinguishing benign from malignant FLLs. MethodsA systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Embase, and Scopus were searched through July 2025 for studies directly comparing MRE and DWI in the same patient cohorts with focal liver lesions, using histopathology or validated imaging follow-up as the reference standard. Sensitivity, specificity, and area under the curve (AUC) were pooled using bivariate random-effects models, with paired analysis to compare modalities. Results219 patients with 284 focal liver lesions were analyzed. MRE demonstrated higher pooled sensitivity (93.8%, 95% CI: 85.6-97.5) and specificity (89.9%, 95% CI: 74.6-96.4) than DWI (sensitivity 86.2%, 95% CI: 80.5-90.5; specificity 83.4%, 95% CI: 74.3-89.8). MRE also had a higher AUC (0.97 vs. 0.88). Likelihood ratio analysis indicated MREs stronger ability to both confirm and exclude malignancy. Paired meta-analysis confirmed a statistically significant increase in sensitivity for MRE (relative sensitivity 1.09; p = 0.018), with no significant difference in specificity. ConclusionMRE demonstrates superior sensitivity and overall diagnostic accuracy compared to DWI for differentiating benign and malignant FLLs. Further large-scale prospective studies are needed to confirm these results and determine optimal cutoff values to guide clinical decision-making.

BackgroundConventional distortion correction techniques include the Reversed Polarity Gradient (RPG) method and FSL-topup, which estimate tissue displacement from EPI images of opposite phase-encoding polarity, and scale image intensity by the Jacobian of the estimated displacement. PurposeTo demonstrate that Jacobian intensity correction (JIC) can cause misleading improvement of EPI image distortion. We propose an alternative distortion correction approach (multi-b RPG; mRPG) that eliminates the JIC factor by normalizing opposite-polarity EPI images across multiple b-values. Study typeRetrospective. Population163 prostate cancer patients without metallic implants. Fieldstrength/Sequence3T diffusion-weighted sequence with EPI readout, using multiple b-values. AssessmentMaps of spatial shift (distortion) were estimated from opposite-polarity EPI volumes using RPG, topup, and mRPG. The estimated spatial shifts from each method were then applied to correct the b=0s/mm2 images (both with and without JIC) and ADC maps (for which JIC is meaningless). Distortion was quantified by the Pearson correlation between opposite-polarity volumes. The distribution of correlation coefficients across all patients was examined for b=0s/mm2 images and ADC maps, before and after distortion correction by each method. The mean, median, and 10th percentile were reported for each distribution. Statistical testsWilcoxon signed-rank tests (=0.05) were used to assess whether correlation increased significantly after distortion correction by each method, and whether mRPG yielded a larger increase versus RPG or topup. ResultsMedian improvement in the correlation between b=0s/mm2 volumes was significantly smaller without JIC (p<0.001): 0.04 vs 0.16 (RPG), 0.06 vs 0.18 (topup). mRPG yielded significantly larger improvements compared to RPG or topup (p<0.001). b=0s/mm2: 0.09 vs 0.04 (RPG) and 0.06 (topup). ADC: 0.09 vs 0.02 (RPG) and 0.03 (topup). Data conclusionDisparity in the distortion-correction performance of conventional methods with and without JIC suggests underestimation of tissue displacement. mRPG shows improved correction of distortion artifacts compared to conventional methods.

We investigated the effectiveness of the most commonly used registration methods (deformable and rigid-body registrations) with different reference images on pharmacokinetic parameters estimated from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of esophageal cancer patients. We obtained DCE-MRI images from 10 patients with esophageal cancer. Both rigid-body and deformable registrations of the images were performed on DCE-MRI images at different time points as reference images before the pharmacokinetic parameters were estimated. The deformable registration used non-rigid B-spline transforms in a multi-resolution scheme, and Euler transform were used for the rigid body registration. A nonparametric statistical test and the intra-class correlation coefficient assessed the consistency and reproducibility of the pharmacokinetic parameters estimated with both registration methods and using images acquired at different time points. Kruskal-Wallis testing demonstrated significant differences (p < 0.05) in all the estimated parameters for deformable registration but no significant differences (p > 0.78) for rigid-body registration. The intra-class correlation coefficient for rigid-body registration was higher than that for deformable registration for each pharmacokinetic parameter, indicating that, for rigid-body registration, the parameter values from different reference images of one patient tended to be similar to each other. In contrast, the values for deformable registration were more variable. In conclusion, the choice of the reference image of deformable registration significantly affected the estimates of pharmacokinetic parameters, and rigid-body registration showed small variations in pharmacokinetic parameters over the choice of the reference images for small motion artifacts of small distal esophageal cancer on DCE-MRI.

Healthy brain aging involves changes in both brain structure and function, including alterations in cellular composition and microstructure across brain regions. Unlike diffusion-weighted MRI (dMRI), diffusion-weighted MR spectroscopy (dMRS) can assess cell-type specific microstructural changes, providing indirect information on both cell composition and microstructure through the quantification and interpretation of metabolites diffusion properties. This work investigates age-related changes in the higher-order diffusion properties of three major intracellular metabolites (N-Acetyl-aspartate, Creatine and Choline) beyond the classical apparent diffusion coefficient in cerebral and cerebellar grey matter of healthy human brain. Twenty-five subjects were recruited and scanned using a diffusion-weighted semi-LASER sequence in two brain regions-of-interest (ROI) at 3T: posterior-cingulate (PCC) and cerebellar cortices. Metabolites diffusion was characterized by quantifying metrics from both Gaussian and non-Gaussian signal representations and biophysical models. All studied metabolites exhibited lower apparent diffusivities and higher apparent kurtosis values in the cerebellum compared to the PCC, likely stemming from the higher microstructural complexity of cellular composition in the cerebellum. Multivariate regression analysis (accounting for ROI tissue composition as a covariate) showed slight decrease (or no change) of all metabolites diffusivities and slight increase of all metabolites kurtosis with age, none of which statistically significant (p>0.05). The proposed age-trajectories provide benchmarks for identifying anomalies in the diffusion properties of major brain metabolites which could be related to pathological mechanisms altering both the brain microstructure and cellular composition.

Human prion diseases are fatal neurodegenerative disorders which cause cognitive impairment and neurological deficits. Additional measures of tissue status are necessary for improving the sensitivity and specificity of clinical diagnosis as in many cases clinical forms of prion disease are commonly mistaken for other forms of dementia. To that effect, we developed a set of quantitative magnetic resonance-based tools, including magnetic resonance spectroscopy (MRS), magnetization transfer ratio (MTR) and quantitative T1 and T2 imaging to study the course of the disease in an animal model of prion disease. Using in vivo MTR, significant changes were detected in the cortex and thalamus of late-stage prion -infected mice as compared to littermates. In addition, we found a significant increase of MTR in thalamus and cortex of 80 dpi healthy mice when compared with 160 dpi healthy mice suggestive of changes occurring during the development of the brain. Using quantitative T2 mapping, significantly higher values were measured in thalamus of prion mice at all stages of the disease (T2=40ms) while T1 was found to be significantly higher in cortex (T1=1.89s) and hippocampus, albeit only in late-stage prion mice as compared to aged-matched controls (T1=1.67s). Using quantitative MRS significant changes were detected in glutamate (Glu) and myo-inositol (Ins) at all stages of prion disease when compared with the control group. NAA, Cr, Lactate and Lipids were only found to be significantly different at early and late stages of the disease while Taurine (Tau) was only significantly increased in the asymptomatic stage without any significant change at early and late stages of the disease. These changes in MRI and MRS signals, which precede clinical signs of disease, could provide insights into the pathogenesis of this disease and may enable early detection of pathology.

BackgroundTumor progression is associated with alterations in tissue mechanical properties. Experimental studies in cancer mechanobiology suggest that increased viscosity of the tumor habitat can promote tumor growth, while malignant tumors often exhibit pronounced mechanical heterogeneity with coexisting soft and rigid regions that facilitate cell motility. Elastography enables noninvasive viscoelastic profiling of soft-tissue properties in vivo and may therefore detect tumor malignancy. PurposeTo investigate whether multiparametric external vibration-based ultrasound time-harmonic elastography (THE) can differentiate benign from malignant liver tumors and identify viscoelastic parameters associated with tumor malignancy. Materials and MethodsIn this prospective study conducted from January 2025 to March 2026, 94 patients with focal liver lesions underwent THE. Eighty-four patients were included in the final analysis (41 benign, 39 malignant; 45 women; age range 30-87 years). Liver and tumor stiffness (shear wave speed; SWS), viscosity (loss angle; {phi}), and spatial mechanical heterogeneity (spatial standard deviation, SWS-SD) were quantified. Diagnostic performance for differentiating benign and malignant tumors was assessed using the area under the receiver operating characteristic curve (AUC). ResultsTumor heterogeneity and surrounding habitat viscosity provided the most pronounced differentiation between malignant and benign lesions. Malignant tumors demonstrated higher SWS-SD (0.41{+/-}0.20 vs. 0.28{+/-}0.11 m/s) and increased {phi} (0.76{+/-}0.09 vs. 0.71{+/-}0.05 rad) with a combined discriminative power of AUC=0.72. These viscoelastic differences were more pronounced in larger tumors of [&ge;]2.5 cm2 area (SWS-SD: 0.47{+/-}0.19 vs. 0.32{+/-}0.11 m/s; {phi}: 0.78{+/-}0.10 vs 0.70{+/-}0.04 rad) yielding AUC=0.88 while excellent discriminative power of AUC=0.97 for [&ge;]6 cm2 tumor area. ConclusionElevated viscosity of the tumor habitat combined with increased tumor stiffness-heterogeneity measured by multiparametric THE can differentiate liver malignancies from benign liver lesions. THE may thus provide a rapid, cost-effective approach for viscoelastic profiling of liver tumors in clinical diagnostic imaging.

PurposeThe purpose of this study was to determine the quantitative variability of diffusion weighted imaging and apparent diffusion coefficient values across a large fleet of MR systems. Using a NIST traceable magnetic resonance imaging diffusion phantom, imaging was reproducible and the measurements were quantitatively compared to known values. MethodsA fleet of 23 clinical MRI scanners was investigated in this study. A NIST/QIBA DWI phantom was imaged with protocols provided with the phantom. The resulting images were analyzed and ADC maps were generated. User-directed region-of-interests on each of the different vials provided ADC measurements among a wide range of known ADC values. ResultsThree diffusion phantoms were used in this study and compared to one another. From the one-way analysis of the variance, the mean and standard deviation of the percent errors from each phantom were not significantly different from one another. The low ADC vials showed larger errors and variation and appear directly related to SNR. Across all the MR systems and data, the coefficient of variation was calculated and Bland-Altman analysis was performed. ADC measurements were similar to one another except for the vials with the lower ADC values, which had a higher coefficient of variation. ConclusionADC values among the three phantoms showed good agreement and were not significantly different from one another. The large percent errors seen primarily at the low ADC values were shown to be a consequence of the SNR dependence and very little bias was observed between magnetic strengths and manufacturers. ADC values between diffusion phantoms were not statistically significant. Future investigations will be performed to study differences in magnetic field strength, vendor, MR system models, gradients, and bore size. More data across different MR platforms would facilitate quantitative measurements for multi-platform and multi-site imaging studies. With the increasing usage of diffusion weighted imaging in the clinic, the characterization of ADC variability for MR systems provides an improved quality control over the MR systems.

Hyperpolarized carbon-13 MRI has shown promise for non-invasive assessment of the cerebral metabolism of [1-13C]pyruvate in both healthy volunteers and in patients. Exchange of pyruvate to lactate catalyzed by lactate dehydrogenase (LDH), and pyruvate flux to bicarbonate through pyruvate dehydrogenase (PDH), are the most widely studied reactions in vivo. Here we show the potential of the technique to probe other metabolic reactions in the human brain. Approximately 50 s after intravenous injection of hyperpolarized pyruvate, high flip angle pulses were used to detect cerebral 13C-labelled carbon dioxide (13CO2), in addition to the 13C-bicarbonate (H13CO2-) subsequently formed by carbonic anhydrase. Brain pH weighted towards the extracellular compartment was calculated from the ratio of H13CO3- to 13CO2 in seven volunteers using the Henderson-Hasselbalch equation, demonstrating an average pH {+/-} S.D. of 7.40 {+/-} 0.02, with inter-observer reproducibility of 0.04. In addition, hyperpolarized [1-13C]aspartate was also detected in four of nine volunteers demonstrating irreversible pyruvate carboxylation to oxaloacetate by pyruvate carboxylase (PC), and subsequent transamination by aspartate aminotransferase (AST), with this flux being approximately 6% of that through PDH. Hyperpolarized [1-13C]alanine signal was also detected within the head but this was localized to muscle tissue in keeping with skeletal alanine aminotransferase (ALT) activity. The results demonstrate the potential of hyperpolarized carbon-13 MRI to assess cerebral and extracerebral [1-13C]pyruvate metabolism in addition to LDH and PDH activity. Non-invasive measurements of brain pH could be particularly important in assessing cerebral pathology given the wide range of disease processes that alter acid-base balance.

Background: Neuromelanin-MRI enables in vivo assessment of the substantia nigra (SN) and locus coeruleus (LC) in individuals with Parkinson's disease (PD), yet longitudinal studies rely on cross-sectional processing that may introduce measurement variability and confound estimates of change over time. Objectives: In this paper, a longitudinal neuromelanin-MRI processing framework is presented that is designed and validated to improve measurement stability and reduce processing-related variability across repeated scans. Methods: Imaging and clinical data from the Quebec Parkinson Network were analyzed in 268 participants (199 PD, 69 controls), including a longitudinal subset of 74 participants (49 PD, 25 controls) scanned approximately one year apart. Validation experiments evaluated slice-by-slice intensity normalization for slice dependent intensity variation, bias field correction for LC signal asymmetry, and the effects of longitudinal registration on measurement stability and PD-control discrimination. Results: Slice-by-slice intensity normalization significantly reduced brainstem intensity variability by 3.6%. A systematic leftward signal asymmetry was observed in the LC and persisted following N4 bias field correction, suggesting a scanner-related effect not captured by conventional bias field modeling. Longitudinal registration reduced annualized change variability by 25-36% for SN_CR and 27-34% for LC_CR metrics in controls, indicating improved within-subject measurement stability. Residual variability was also reduced for contrast-based metrics by up to 28%. Longitudinal registration generally produced larger PD-control effect sizes at baseline and follow-up, particularly for SN volume metrics. However, no significant method x group x time interactions were observed, indicating that estimated longitudinal trajectories did not differ significantly between longitudinal and conventional cross-sectional processing. Conclusions: Longitudinal registration reduced technical variability and improved the precision of NM-MRI measurements. Although it did not significantly enhance detection of longitudinal PD-control differences over the follow-up interval examined here, it provides a more robust framework for longitudinal NM-MRI studies and may improve sensitivity to subtler biological effects in future investigations.

Magnetic resonance imaging (MRI) of focal or diffuse myelin damage or remyelination may provide important insights into disease progression and potential treatment efficacy in multiple sclerosis (MS). We performed post-mortem MRI and histopathological myelin measurements in seven progressive MS cases to evaluate the ability of three myelin-sensitive MRI scans to distinguish different stages of MS pathology, particularly chronic demyelinated and remyelinated lesions. At 3 Tesla, we acquired two different myelin water imaging (MWI) scans and magnetization transfer ratio (MTR) data. Histopathology included histochemical stainings for myelin phospholipids (LFB) and iron as well as immunohistochemistry for myelin proteolipid protein (PLP), CD68 (phagocytosing microglia/macrophages) and BCAS1 (remyelinating oligodendrocytes). Mixed-effects modelling determined which histopathological metric best predicted MWF and MTR in normal appearing and diffusely abnormal white matter, slowly expanding, inactive, remyelinated and ischemic lesions. Both MWI measures correlated well with each other and histology across regions, reflecting the different stages of MS pathology. MTR data showed a considerable influence of components other than myelin and a strong dependency on tissue storage duration. Both MRI and histology revealed increased myelin densities in inactive compared with slowly expanding lesions. Chronic inactive lesions harboured single scattered myelin fibres indicative of low-level remyelination. Mixed-effects modelling showed that smaller differences between white matter areas were linked to PLP densities and only to a smaller extent confounded by iron. MWI reflects differences in myelin lipids and proteins across all levels of myelin densities encountered in MS, including low-level remyelination in chronic inactive lesions.

PurposeNeurite orientation dispersion and density imaging (NODDI) provides measures of neurite density and dispersion through computation of the neurite density index (NDI) and the orientation dispersion index (ODI). However, NODDI overestimates the cerebrospinal fluid water fraction in white matter (WM) and provides physiologically unrealistic high NDI values. Furthermore, derived NDI values are echo time (TE)-dependent. In this work, we propose a modification of NODDI, named constrained NODDI (C-NODDI), for NDI and ODI mapping in WM. MethodsUsing NODDI and C-NODDI, we investigated age-related alterations in WM in a cohort of 58 cognitively unimpaired adults. Further, NDI values derived using NODDI or C-NODDI were correlated with the neurofilament light chain (NfL) concentration levels, a plasma biomarker of axonal degeneration. ResultsODI derived values using both approaches were virtually identical. We confirm the previous finding that NDI estimation using NODDI is TE-dependent. In contrast, C-NODDI-NDI exhibit lower susceptibility to TE. Further, C-NODDI-NDI values were lower than NODDI-NDI. Further, our results indicate a quadratic relationship between NDI and age suggesting that axonal maturation continues until middle age followed by a decrease. This quadratic association was notably significant in several WM regions using C-NODDI, while limited to a few regions using NODDI. ODI exhibited overall constant trends with age. Finally, C-NODDI-NDI values exhibited a stronger correlation with NfL concentration levels as compared NODDI-NDI, with lower NDI values correspond to higher levels of NfL. ConclusionsC-NODDI provides a complementary method to NODDI for determination of NDI in white matter in normative aging.

Breast cancer screening is necessary to reduce mortality due to undetected breast cancer. Current methods have limitations, and as a result many women forego regular screening. Magnetic resonance imaging (MRI) can overcome most of these limitations, but access to conventional MRI is not widely available for routine annual screening. Here, we used an MRI scanner operating at ultra-low field (ULF) to image the left breasts of 11 women (mean age, 35 years {+/-}13 years) in the prone position. Three breast radiologists reviewed the imaging and were able to discern the breast outline and distinguish fibroglandular tissue (FGT) from intramammary adipose tissue. Additionally, the expert readers agreed on their assessment of the breast tissue pattern including fatty, scattered FGT, heterogeneous FGT, and extreme FGT. This preliminary work demonstrates that ULF breast MRI is feasible and may be a potential option for comfortable, widely deployable, and low-cost breast cancer diagnosis and screening.

ObjectiveTo investigate the metabolic pattern of different types of iron accumulation in multiple sclerosis (MS) lesions, and compare metabolic alterations within and at the periphery of lesions and newly emerging lesions in vivo according to iron deposition. Methods7T MR spectroscopic imaging and susceptibility-weighted imaging was performed in 31 patients with relapsing-remitting MS (16 female/15 male; mean age, 36.9 {+/-} 10.3 years). Mean metabolic ratios of four neuro-metabolites were calculated for regions of interest (ROI) of normal appearing white matter (NAWM), "non-iron" (lesion without iron accumulation on SWI), and three distinct types of iron-laden lesions ("rim": distinct rim-shaped iron accumulation; "area": iron deposition across the entire lesions; "transition": transition between "area" and "rim" accumulation shape), and for lesion layers of "non-iron" and "rim" lesions. Furthermore, newly emerging "non-iron" and "iron" lesions were compared longitudinally, as measured before their appearance and one year later. ResultsThirty-nine of 75 iron-containing lesions showed no distinct paramagnetic rim. Of these, "area" lesions exhibited a 65% higher mIns/tNAA (p=0.035) than "rim" lesions. Comparing lesion layers of both "non-iron" and "rim" lesions, a steeper metabolic gradient of mIns/tNAA ("non-iron" +15%, "rim" +40%) and tNAA/tCr ("non-iron" -15%, "rim" -35%) was found in "iron" lesions, with the lesion core showing +22% higher mIns/tNAA (p=0.005) and -23% lower tNAA/tCr (p=0.048) in "iron" compared to "non-iron" lesions. In newly emerging lesions, 18 of 39 showed iron accumulation, with the drop in tNAA/tCr after lesion formation remaining significantly lower compared to pre-lesional tissue over time in "iron" lesions (year 0: p=0.013, year 1: p=0.041) as opposed to "non-iron" lesions (year 0: p=0.022, year 1: p=0.231). Conclusion7T MRSI allows in vivo characterization of different iron accumulation types each presenting with a distinct metabolic profile. Furthermore, the larger extent of neuronal damage in lesions with a distinct iron rim was reconfirmed via reduced tNAA/tCr concentrations, but with metabolic differences in lesion development between (non)-iron-containing lesions. This highlights the ability of MRSI to further investigate different types of iron accumulation and suggests possible implications for disease monitoring. Key pointsO_LIIron-containing lesions were suggested as a biomarker for tissue damage, a more aggressive disease course, and worse clinical outcome, but related metabolic alterations are poorly understood. C_LIO_LIOur MRSI results confirm a higher extent of tissue damage within paramagnetic rim lesions reflected by reduced tNAA/tCr. Forty-six percent of newly emerging lesions showed an iron accumulation, correlating with an altered metabolic behavior compared to non-iron lesions. C_LIO_LIOnly forty-eight percent of iron-containing lesions have a distinct rim-shaped iron accumulation, although most studies focus on these paramagnetic rim lesions. Our results show highly different metabolic profiles (especially with regard to mIns/tNAA and tNAA/tCr) within different iron accumulation types, highlighting the need for distinct classification of iron accumulation in future studies. C_LI

IntroductionMagnetic resonance spectroscopy (MRS) of the brain offers significant potential for monitoring metabolic alterations associated with neurological pathologies. However, to date, its application has predominantly been limited to research settings and a select number of clinical centers. This study aimed to assess the diagnostic accuracy of brain MRS in detecting various neurological diseases. MethodsBrain MRS examinations conducted at public hospitals affiliated with Shiraz University, Iran, from 2021 to 2024 were retrospectively collected. The findings, as reported by attending radiologists, were compared with the final clinical or histopathological diagnoses of the patients. Diagnostic performance metrics, including sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy, were calculated. ResultsBrain MRS correctly identified the pathology in 61% of cases. The technique demonstrated high specificity, positive predictive value, negative predictive value, and overall accuracy--each exceeding 90%--across a range of brain pathologies. These included both primary and secondary tumoral processes, as well as non-tumoral conditions such as pyogenic brain abscess, toxoplasmosis, demyelinating diseases, and encephalitis. However, sensitivity varied considerably, ranging from 33% to 100%, with the lowest sensitivity observed in cases of pyogenic brain abscesses, brain hemorrhages, and central nervous system (CNS) vasculitis. ConclusionThis study indicates that certain neurological pathologies may exhibit atypical spectroscopic features that are not yet fully characterized. The findings underscore the necessity for further research involving larger patient populations to better delineate the spectroscopic patterns associated with these conditions.