Changes In T2 Research Articles

Quantitative muscle MRI combined with AI-based segmentation as a follow-up biomarker for ATTRv patients: A longitudinal pilot study.

Intramuscular fat fraction (FF), assessed using quantitative MRI (qMRI), has emerged as a promising biomarker for hereditary transthyretin amyloidosis (ATTRv) patients. Currently, the main drawbacks to its use in future therapeutic trials are its sensitivity to change over a short period of time and the time-consuming manual segmentation step to extract quantitative data. This pilot study aimed to demonstrate the suitability of an Artificial Intelligence-based (AI) segmentation technique to assess disease progression in a real-life cohort of ATTRv patients over 1 year. Fifteen ATTRv patients were included in this monocentric, observational, prospective study. FF, magnetization transfer ratio (MTR), and quantitative T2 were extracted from patients' lower limb qMRI at two time points, 1 year apart, at thigh and leg levels. qMRI parameters were correlated with clinical and electrophysiological parameters assessed at the same time. Global FF at leg level significantly progressed over 1 year: +1.28 ± 2.62% (p = 0.017). At thigh level, no significant change in global FF, MTR, or T2 was measured. The leg FF was strongly correlated with the main clinical and electrophysiological scores. AI-based CNN network segmentation combined with qMRI can be used to obtain quantitative metrics for longitudinal studies in ATTRv patients. Global FF at the leg level seems to be the most sensitive MRI biomarker to track disease progression in a 1-year period. Larger studies with treatment-specific groups will now be necessary to determine the place of qMRI markers compared to the current clinical and electrophysiological scores.

NIMG-85. RADIATION DOSE IS ASSOCIATED WITH CHANGE IN MAGNETIC RESONANCE FINGERPRINTING PROPERTIES OF ANATOMICALLY DISTINCT REGIONS OF INTEREST IN GLIOBLASTOMA MULTIFORME PATIENTS

Abstract Magnetic Resonance Fingerprinting (MRF) is an investigational imaging technique that provides spatially-resolved quantification of tissue properties, in contrast to qualitatively weighted conventional MR imaging. Intentional sequential variation of acquisition parameters throughout the MRF acquisition produces a unique quantitative signal timecourse for each tissue, which generates a spatial “fingerprint” for individual voxels. This study applies MRF to quantitatively correlate radiation dose with MR signal intensity changes, specifically T1, T2, and M0 maps across regions of interest (ROIs) that are involved in cognitive speed and processing. Three patients who underwent radiation therapy for resected glioblastoma multiforme participated in this study. MRF scans were conducted at pre-radiotherapy (pre-RT), mid-radiotherapy (mid-RT), and post-radiotherapy (post-RT) timepoints. ROIs (bilateral hippocampi, amygdalae, dorsolateral prefrontal cortices, and corpus callosum) were contoured and radiation dose to the ROI contours at mid-RT and post-RT timepoints were obtained using MIM treatment planning software (MIM Software, Beachwood, OH). Spearman’s rank correlation test was conducted in MATLAB (MATLAB R2024a, Natick, MA) for mean radiation dose to ROIs against MRF T1 relaxation time, T2 relaxation time, and M0 proton density. Mean radiation dose exhibited statistically significant correlation with absolute changes from pre-RT to post-RT T1 relaxation time, T2 relaxation time, and M0 proton density values across the ROIs. Mid-RT scans showed intermediate changes, suggesting a progressive alteration in tissue characteristics with accumulating radiation dose. The hippocampus and amygdala received lower radiation doses than other ROIs and exhibited less pronounced changes in T1, T2, and M0 values. These results demonstrate a novel application of MRF in quantitative characterization of imaging changes in anatomically distinct ROIs. The correlation between radiation dose and absolute changes in MRF signal values from pre-RT to post-RT MRF scans reflect progressive changes as a result of radiation exposure.

Longitudinal Assessment of T1 Mapping Trends Disease in Pediatric Patients With Heart Transplant.

Surveillance for heart transplant rejection by endomyocardial biopsy is invasive and may yield false negatives. T1 and T2 mapping from cardiac magnetic resonance can demonstrate elevations with rejection. We sought to evaluate longitudinal changes in T1 and T2 mapping in pediatric patients with heart transplant. A cohort study was performed of pediatric patients with heart transplant who underwent concurrent endomyocardial biopsy and cardiac magnetic resonance with T1 and T2 mapping from December 2019 to July 2024. Segmental values were measured and subsegmental elevations (ie, hotspots) were identified. Subjects were categorized as either treated rejection or no rejection. Peak and mean T1 and T2 values and number of hotspots at/between each time point for patient dyads were compared between the groups. A total of 21 subjects (7 treated rejection, 14 no rejection) with 68 total encounters met inclusion criteria. Peak and mean T1 values were higher in treated rejection patients during the rejection period and decreased with treatment (peak, 1086 versus 1052; mean, 1028 versus 1021), such that at last follow-up when their rejection had resolved, there was no significant difference in values when compared with no rejection patients (peak, 1066; mean, 1016). The number of T1 hotspots decreased after rejection treatment (2 versus 1). There were no changes in peak or mean T2 values in the treated rejection group despite treatment, and peak and mean T2 values were similar to patients with no rejection through last follow-up. Elevated T1 values and hotspots observed during cardiac allograft rejection decline in response to treatment. Cardiac magnetic resonance may serve as a noninvasive monitoring tool for the development and resolution of rejection, as well as the effectiveness of rejection therapy.

Metabolite T2 relaxation times decrease across the adult lifespan in a large multi-site cohort.

Relaxation correction is crucial for accurately estimating metabolite concentrations measured using in vivo MRS. However, the majority of MRS quantification routines assume that relaxation values remain constant across the lifespan, despite prior evidence of T2 changes with aging for multiple of the major metabolites. Here, we comprehensively investigate correlations between T2 and age in a large, multi-site cohort. We recruited approximately 10 male and 10 female participants from each decade of life: 18-29, 30-39, 40-49, 50-59, and 60+ y old (n = 101 total). We collected PRESS data at eight TEs (30, 50, 74, 101, 135, 179, 241, and 350 ms) from voxels placed in white-matter-rich centrum semiovale (CSO) and gray-matter-rich posterior cingulate cortex (PCC). We quantified metabolite amplitudes using Osprey and fit exponential decay curves to estimate T2. Older age was correlated with shorter T2 for tNAA2.0, tCr3.0, tCr3.9, tCho, and tissue water (CSO and PCC), as well as mI and Glx (PCC only); rs = -0.22 to -0.63, all p < 0.05, false discovery rate (FDR)-corrected. These associations largely remained statistically significant when controlling for cortical atrophy. By region, T2 values were longer in the CSO for tNAA2.0, tCr3.9, Glx, and tissue water and longer in the PCC for tCho and mI. T2 did not differ by region for tCr3.0. These findings underscore the importance of considering metabolite T2 differences with aging in MRS quantification. We suggest that future 3T work utilize the equations presented here to estimate age-specific T2 values instead of relying on uniform default values.

Accelerated 2D radial Look-Locker T1 mapping using a deep learning-based rapid inversion recovery sampling technique.

Efficient abdominal coverage with T1-mapping methods currently available in the clinic is limited by the breath hold period (BHP) and the time needed for T1 recovery. This work develops a T1-mapping framework for efficient abdominal coverage based on rapid T1 recovery curve (T1RC) sampling, slice-selective inversion, optimized slice interleaving, and a convolutional neural network (CNN)-based T1 estimation. The effect of reducing the T1RC sampling was evaluated by comparing T1 estimates from T1RC ranging from 0.63 to 2.0s with reference T1 values obtained from T1RC =2.5-5s. Slice interleaving methodologies were evaluated by comparing the T1 variation in abdominal organs across slices. The repeatability of the proposed framework was demonstrated by performing acquisition on test subjects across imaging sessions. Analysis of in vivo data based on retrospectively shortening the T1RC showed that with the CNN framework, a T1RC =0.84 s yielded T1 estimates without significant changes in mean T1 (p> 0.05) or significant increase in T1 variability (p> 0.48) compared to the reference. Prospectively acquired data using T1RC =0.84 s, an optimized slice interleaving scheme, and the CNN framework enabled 21 slices in a 20 s BHP. Analyses across abdominal organs produced T1 values within 2% of the reference. Repeatability experiments yielded Pearson's correlation, repeatability coefficient, and coefficient of variation of 0.99, 2.5%, and 0.12%, respectively. The proposed T1 mapping framework provides full abdominal coverage within a single BHP.

Use of multiparametric MRI to noninvasively assess iodinated contrast-induced acute kidney injury

PurposeTo gauge the utility of multiparametric MRI in characterizing pathologic changes after iodinated contrast-induced acute kidney injury (CI-AKI) in rats. MethodsWe randomly grouped 24 rats injected with 8 g iodine/kg of body weight (n = 6 each) and 6 rats injected with saline as controls. All rats underwent T1, T2 mapping and diffusion kurtosis imaging (DKI) after contrast injection at 0 (control), 1, 3, 7, 13 days. T1, T2, and mean kurtosis (MK) values were performed in renal outer/inner stripes of outer medulla (OSOM and ISOM) and cortex (CO), and their diagnosis performance for CI-AKI also been evaluated. Serum creatinine (SCr), insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor metalloproteinase 2 (TIMP-2), aquaporin-1 (AQP1), α-smooth muscle actin (α-SMA), and histologic indices were examined. ResultsCompared with controls, urinary concentrations of both TIMP-2 and IGFBP7 were obviously elevated from Day 1 to Day 13 (all p < 0.05). T2 values were significantly higher than control group for Days 1 and 3, and T1 and MK increased were more remarkable at all time points (Days 1–13) in CI-AKI (all p < 0.05) than control group. Changes in T1 and MK strongly correlated with renal injury scores of all anatomical compartments and with expression levels of AQP1 and moderately correlated with α-SMA. Changes in T2 values correlating moderately with renal scores of CO, ISOM and OSOM and AQP1. The MK obtained the highest area under the receiver operating characteristic (ROC) curve of 0.846 with a sensitivity of 70.8 % and specificity of 88.9 %. ConclusionsCombined use of multiparametric MRI could be a valid noninvasive method for comprehensive monitoring of CI-AKI. Among these parameters, MK may achieve the best diagnostic performance for CI-AKI.

Application of H2N-Fe3O4 Nanoparticles for Prostate Cancer Magnetic Resonance Imaging in an Animal Model.

This paper presents the efficacy of a contrast agent based on H2N-Fe3O4 nanoparticles for the detection of prostate cancer in an animal model using a preclinical 9.4 T MRI system. The relaxivities r1 and r2 of the nanoparticles were 6.31 mM-1s-1 and 8.33 mM-1s-1, respectively. Nanoparticles injected in a concentration of 2 mg Fe/mL decreased the tumor-relative T1 relaxation across all animals from 100 to 76 ± 26, 85 ± 27, 89 ± 20, and 97 ± 16 12 min 1 h, 2 h, and 24 h post injection, respectively. The corresponding T1 decrease in muscle tissues was 90 ± 20, 94 ± 23, 99 ± 12, and 99 ± 14. The relative T2 changes in the tumor were 82 ± 17, 89 ± 19, 97 ± 14, and 99 ± 8 12 min, 1 h, 2 h, and 24 h post injection, respectively, while, for muscle tissues, these values were 95 ± 11, 95 ± 8, 97 ± 6, and 95 ± 10 at the corresponding time points. The differences in the relative T1 and T2 were only significant 12 min after injection (p < 0.05), although a decrease was visible at each time point, but it was statistically insignificant (p > 0.05). The results showed the potential application of H2N-Fe3O4 nanoparticles as contrast agents for enhanced prostate cancer MRI.

The additional value of myocardial T1ρ mapping to T1 and T2 mapping for predicting subsequent cancer therapy-related cardiac dysfunction in breast cancer patients who received anthracyclines with/without trastuzumab

ObjectivesWe aimed to describe changes in parameters derived from myocardial T1ρ, T1, and T2 mapping and assess whether incorporating T1ρ mapping improves the predictive performance of T1 and T2 mapping for subsequent cancer therapy-related cardiac dysfunction (CTRCD) in breast cancer patients treated with anthracyclines with/without trastuzumab. MethodsFrom March 2021 to May 2023, 82 participants with breast cancer treated with anthracyclines with/without trastuzumab were prospectively recruited. Cardiac magnetic resonance was performed at baseline, 3 and 6 months in relation to baseline. T1ρ, T1 and T2 values were measured and compared by repeated measures analyses of variance. Logistic regression and receiver operating characteristic analysis were used to assess the performance in predicting subsequent CTRCD. ResultsNineteen (23.17 %) participants developed CTRCD. T1ρ and T1 values progressively increased over time (all p < 0.001), while T2 values increased at 3 (p < 0.001 and p = 0.002, respectively) and 6 months (all p < 0.001) compared to baseline in both the CTRCD (+) and CTRCD (−) groups. The changes in T1ρ (OR, 3.892, p = 0.003) and T1 (OR, 1.082, p = 0.002) from baseline to 3 months were associated with subsequent CTRCD. The combination of the changes in T1ρ and T1 from baseline to 3 months obtained an improved area under the curve of 0.853. ConclusionT1ρ, T1 and T2 increased after treatment of anthracyclines with/without trastuzumab. Myocardial T1ρ mapping provides additional predictive value to T1 mapping for subsequent CTRCD in breast cancer patients who received anthracyclines with/without trastuzumab. Clinical relevance statementMyocardial T1ρ mapping offers additional predictive value to T1 and T2 mapping for subsequent CTRCD in breast cancer patients who received anthracyclines with/without trastuzumab. This may facilitate accurate prediction of cardiotoxicity and personalized treatment decision making in breast cancer.

CRISPR/Cas12a and Hybridization Chain Reaction-Coregulated Magnetic Relaxation Switching Biosensor for Sensitive Detection of Viable Salmonella in Animal-Derived Foods.

We combined a CRISPR/Cas12a system with a hybridization chain reaction (HCR) to develop an ultrasensitive magnetic relaxation switching (MRS) biosensor for detecting viable Salmonella typhimurium (S. typhimurium). Magnetic nanoparticles of two sizes (30 and 1000 nm: MNP30 and MNP1000, respectively) were coupled through HCR. The S. typhimurium gene-activated CRISPR/Cas12a system released MNP30 from the MNP1000-HCR-MNP30 complex through a trans-cleavage reaction. After magnetic separation, released MNP30 was collected from the supernatant and served as a transverse relaxation time (T2) signal probe. Quantitative detection of S. typhimurium is achieved by establishing a linear relationship between the change in T2 and the target gene. The biosensor's limit of detection was 77 CFU/mL (LOD = 3S/M, S = 22.30, M = 0.87), and the linear range was 102-108 CFU/mL. The accuracy for detecting S. typhimurium in real samples is comparable to that of qPCR. Thus, this is a promising method for the rapid and effective detection of foodborne pathogens.

External Focus of Attention Reduces Cartilage Load During Drop Landings.

The aim of the present study was to examine the effects of attentional focus instructions on acute changes in the transverse relaxation time (T2) of the femorotibial cartilage and in cartilage volume during repeated drop-jump landings. Ten healthy females (Mage = 20.4 ± 0.8 years) performed a drop landing task from a 50 cm high box over the course of 3 days (50 repetitions each day) across three attentional focus conditions: external focus (EF: focus on landing as soft as possible), internal focus (IF: focus on bending your knees when you land), and control (CON: no-focus instruction), which was counterbalanced across focus conditions. T2 mapping and the volume of femorotibial cartilage were determined from magnetic resonance imaging scans at 1.5 T for the dominant knee before and after completing the drop landings in each attentional focus condition per day. Results indicated a smaller change in cartilage T2 relaxation time and volumetry in the central load-bearing lateral cartilage under the EF, compared to IF and CON. Moreover, the change in T2 and cartilage volume was greater for lateral tibial cartilage as compared to femoral cartilage and was independent of attentional focus instructions. No significant acute quantitative changes were observed in the medial compartment. The peak vertical ground reaction force was found to be the lowest under the EF, compared to IF and CON. These findings suggest that external focus of attention may reduce cartilage load, potentially aiding in the control or management of cartilage injuries during landing in female athletes.

T1 Mapping of the Abdomen, From the AJR "How We Do It" Special Series.

By exploiting different tissues' characteristic T1 relaxation times, T1-weighted images help distinguish normal and abnormal tissues, aiding assessment of diffuse and local pathologies. However, such images do not provide quantitative T1 values. Advances in abdominal MRI techniques have enabled measurement of abdominal organs' T1 relaxation times, which can be used to create color-coded quantitative maps. T1 mapping is sensitive to tissue microenvironments including inflammation and fibrosis and has received substantial interest for noninvasive imaging of abdominal organ pathology. In particular, quantitative mapping provides a powerful tool for evaluation of diffuse disease by making apparent changes in T1 occurring across organs that may otherwise be difficult to identify. Quantitative measurement also facilitates sensitive monitoring of longitudinal T1 changes. Increased T1 in liver helps to predict parenchymal fibro-inflammation, in pancreas is associated with reduced exocrine function from chronic or autoimmune pancreatitis, and in kidney is associated with impaired renal function and aids diagnosis of chronic kidney disease. In this review, we describe the acquisition, postprocessing, and analysis of T1 maps in the abdomen and explore applications in liver, spleen, pancreas, and kidney. We highlight practical aspects of implementation and standardization, technical pitfalls and confounding factors, and areas of likely greatest clinical impact.

Baseline-to-loaded changes in regional tibial cartilage thickness, T1ρ and T2: Utilization of an MRI compatible loading device.

The objective of the study was to evaluate tibial cartilage thickness (TCT), T1ρ and T2 values within both loaded and baseline configurations in a cadaveric knee model using a 3D bone based tibial coordinate system. Ten intact cadaveric knees were mounted into an magnetic resonance imaging (MRI) compatible loading device. Morphologic and quantitative MRI (qMRI) images were acquired with the knee in a baseline configuration and after application of 50% body weight. The morphologic images were evaluated for cartilage degeneration using a modified Noyes scoring system. A 3D bone-based tibial coordinate system was utilized to evaluate regional changes of tibial T1ρ, T2, and cartilage thickness values among regions covered and uncovered by the meniscus. Inter-regional differences in medial and lateral MRI outcomes were found between loaded and baseline configurations. Cartilage regions covered by the meniscus demonstrated disparate qMRI and TCT results as compared to cartilage regions not covered by the meniscus. The regions covered by meniscus experienced a ~3.5%, ~0.5%, and ~5.5% reduction of T1ρ (p < 0.05, medial and lateral compartments), T2 and TCT, respectively, in both compartments while regions not covered by the meniscus experienced larger reductions of ~10%, ~2%, and ~10.5% reduction of T1ρ (p < 0.05, medial and lateral compartments), T2 and TCT (p < 0.05, lateral compartment only), respectively, in both compartments. T1ρ and T2 decreases following application of 50% body weight load were substantially larger in the tibial regions with modified Noyes grade 3 (n = 2) compared to either healthy regions (n = 85, p < 0.0.003) or regions with modified Noyes grade 2 (n = 13, p < 0.004). Interregional differences in MRI outcomes reflect variations in structure and function, and largely followed a pattern in cartilage regions that were covered or not covered by the meniscus. Results of the current study suggest that ΔT1ρ and ΔT2 values may be sensitive to superficial fissuring, more than baseline or loaded T1ρ or T2 values, or TCT alone, however future studies with additional specimens, with greater variability in OA grade distribution, may further emphasize the current findings.

Immunologic analysis of CSF in patients with de novo diagnosed RRMS. The role of chemokines in the early phase of the disease

Objectives: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by demyelination and neurodegeneration. Chemokines regulate leukocyte migration and inflammation in MS. In the present study, we evaluated selected chemokine levels in the cerebrospinal fluid of patients with multiple sclerosis diagnosed de novo compared to healthy controls.Methods: We measured EOTAXIN, IP-10, MCP-1, MIP-1a, MIP-1b and RANTES in the cerebrospinal fluid of 118 patients with de novo RRMS and 112 controls, analyzing correlations with time from symptom onset to diagnosis and changes in MRI.Results: Higher levels of EOTAXIN, IP-10, MIP-1B and RANTES, and lower MCP-1 were observed in MS patients compared to controls. MIP-1A did not show statistical significance. EOTAXIN and IP-10 concentrations increased with time. RANTES concentration correlated positively with T2 changes in MRI of the cervical spine, and EOTAXIN concentration correlated negatively with gadolinium (Gd+) changes in the cervical spine. There was no correlation with changes in the thoracic spine or brain.Conclusions: Chemokines play a significant role in the early phase of MS by influencing inflammatory activity. They may represent potential therapeutic targets for the treatment of this disease.

Evaluating the therapeutic effect of LIPUS in the early stage of traumatic brain injury using FA and T2* in rats.

To evaluate the protective effect of LIPUS at the early stage of brain trauma in rats, 45 rats were randomly divided into 3 groups: sham (n = 15), TBI (n = 15) and LIPUS treatment groups (n = 15). Ipsilateral and contralateral cortical and thalamic parameters obtained by diffusion tensor imaging (DTI) and fast low-angle shot magnetic resonance imaging (FLASH-MRI) were measured at different times after trauma. For fractional anisotropy (FA) and T2* values, two-way repeated measures ANOVA with Tukey's post hoc was used for intergroup comparisons. With observation time prolonged, the FA values of the ipsilateral cortex in the TBI group gradually increased and were significantly higher than those in the LIPUS treatment group on Day 7 (adjusted P = 0.0067). FA values in the contralateral cortex decreased at this time and were significantly lower than those in the LIPUS treatment group (adjusted P = 0.0192). Meanwhile, compared with LIPUS group, FA values were significantly higher in the injured thalamus (adjusted P = 0.0025). Combined with correlation analysis, FA values were positively correlated with neuronal damage (P = 0.0148, r2 = 0.895). At 7 days after trauma, T2* values in the ipsilateral cortex of the TBI group were significantly lower. After analysis of ferritin content and correlation, we found that T2* values were negatively correlated with ferritin (P = 0.0259, r2 = -0.849). By measuring post-traumatic changes in FA and T2* values, it is possible to demonstrate a neuronal protective effect of LIPUS in the early phase of TBI rats and promote brain rehabilitation.

Mineralocorticoid Receptor Antagonism Prevents Aortic Plaque Progression and Reduces Left Ventricular Mass and Fibrosis in Patients With Type 2 Diabetes and Chronic Kidney Disease: The MAGMA Trial.

Persistent mineralocorticoid receptor activation is a pathologic response in type 2 diabetes and chronic kidney disease. Whereas mineralocorticoid receptor antagonists are beneficial in reducing cardiovascular complications, direct mechanistic pathways for these effects in humans are lacking. The MAGMA trial (Mineralocorticoid Receptor Antagonism Clinical Evaluation in Atherosclerosis) was a randomized, double-blind, placebo-controlled trial in patients with high-risk type 2 diabetes with chronic kidney disease (not receiving dialysis) on maximum tolerated renin-angiotensin system blockade. The primary end point was change in thoracic aortic wall volume, expressed as absolute or percent value (ΔTWV or ΔPWV), using 3T magnetic resonance imaging at 12 months. Secondary end points were changes in left ventricle (LV) mass; LV fibrosis, measured as a change in myocardial native T1; and 24-hour ambulatory and central aortic blood pressures. Tertiary end points included plasma proteomic changes in 7596 plasma proteins using an aptamer-based assay. A total of 79 patients were randomized to placebo (n=42) or 25 mg of spironolactone daily (n=37). After a modified intent-to-treat, including available baseline data of study end points, patients who completed the trial protocol were included in the final analyses. At the 12-month follow-up, the average change in PWV was 7.1±10.7% in the placebo group and 0.87±10.0% in the spironolactone group (P=0.028), and ΔTWV was 1.2±1.7 cm3 in the placebo group and 0.037±1.9 cm3 in the spironolactone group (P=0.022). Change in LV mass was 3.1±8.4 g in the placebo group and -5.8±8.4 g in the spironolactone group (P=0.001). Changes in LV T1 values were significantly different between the placebo and spironolactone groups (26.0±41.9 ms in the placebo group versus a decrease of -10.1±36.3 ms in the spironolactone group; P=6.33×10-4). Mediation analysis revealed that the spironolactone effect on thoracic aortic wall volume and myocardial mass remained significant after adjustment for ambulatory and central blood pressures. Proteomic analysis revealed a dominant effect of spironolactone on pathways involving oxidative stress, inflammation, and leukocyte activation. Among patients with diabetes with moderate to severe chronic kidney disease at elevated cardiovascular risk, treatment with spironolactone prevented progression of aortic wall volume and resulted in regression of LV mass and favorable alterations in native T1, suggesting amelioration of left-ventricular fibrosis. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02169089.

T1 relaxation and axon fibre configuration in human white matter.

Understanding the effects of white matter (WM) axon fibre microstructure on T1 relaxation is important for neuroimaging. Here, we have studied the interrelationship between T1 and axon fibre configurations at 3T and 7T. T1 and S0 (=signal intensity at zero TI) were computed from MP2RAGE images acquired with six inversion recovery times. Multishell diffusion MRI images were analysed for fractional anisotropy (FA); MD; V1; the volume fractions for the first (f1), second (f2) and third (f3) fibre configuration; and fibre density cross-section images for the first (fdc1), second (fdc2) and third (fdc3) fibres. T1 values were plotted as a function of FA, f1, f2, f3, fdc1, fdc2 and fdc3 to examine interrelationships between the longitudinal relaxation and the diffusion MRI microstructural measures. T1 values decreased with increasing FA, f1 and f2 in a nonlinear fashion. At low FA values (from 0.2 to 0.4), a steep shortening of T1 was followed by a shallow shortening by 6%-10% at both fields. The steep shortening was associated with decreasing S0 and MD. T1 also decreased with increasing fdc1 values in a nonlinear fashion. Instead, only a small T1 change as a function of either f3 or fdc3 was observed. In WM areas selected by fdc1 only masks, T1 was shorter than in those with fdc2/fdc3. In WM areas with high single fibre populations, as delineated by f1/fdc1 masks, T1 was shorter than in tissue with high complex fibre configurations, as segmented by f2/fdc2 or f3/fdc3 masks. T1 differences between these WM areas are attributable to combined effects by T1 anisotropy and lowered FA. The current data show strong interrelationships between T1, axon fibre configuration and orientation in healthy WM. It is concluded that diffusion MRI microstructural measures are essential in the effort to interpret quantitative T1 images in terms of tissue state in health and disease.

Platelet-Rich Plasma for Patellar Tendinopathy: A randomized controlled trial correlating clinical outcomes and quantitative imaging

Abstract Background Patellar tendinopathy (PT) is a common overuse injury in active individuals, often with incomplete recovery. Recently, platelet-rich plasma (PRP) treatment has shown promising results. Traditional qualitative markers are not reliable indicators of treatment response. Advanced quantitative imaging, such as Ultrashort-TE (UTE) MRI and ultrasound (US) shear-wave elastography (SWE) may be valuable adjuncts. Purpose To investigate the clinical outcomes and quantitative imaging changes in adults with symptomatic patellar tendinopathy treated with PRP, needle tenotomy (NT) or sham injection (SH). Materials and Methods Single-blinded prospective randomized controlled trial from April 2017 until July 2022 with three parallel interventions in athletes with symptomatic PT: PRP, NT and SH. VAS pain, VISA-P function, conventional US, shear wave speed (SWS), UTE T2* relaxation time (T2*single) and T2* fraction of fast-relaxing macromolecular-bound water (FF) were acquired at 0, 16 and 52-weeks. Longitudinal analyses were used to compare intra- and inter-group differences over time. Correlations were assessed by Pearson’s correlation coefficient. Results 29 subjects (mean age, 26.1±5.3 years; 82.8% men) were randomized. At 52-weeks all groups demonstrated a significant improvement in pain, though most pronounced within the PRP group (ΔVAS=-5.9, 95% confidence interval (CI) [-7.8, -3.9], p&amp;lt;.001). SWS increased significantly only in the PRP group (Δ+2.3, [0.8, 3.9], p=.003). Change in SWS was moderately correlated with change in pain across all groups (r=-.52, [-.76, -.15], p=.009). FF significantly increased in all groups (Δ=0.10-0.11, p=.024-0.046); a significant decrease in T2*single was only seen in the PRP group (Δ=-8.07, [-14.6, -1.55], p=.014). Conclusion Clinical improvement was evident irrespective of treatment but was greatest with PRP. SWS correlated with improvement in pain and may represent an adjunctive measure to assess healing in patellar tendinopathy. Correlative changes in T2* UTE quantitative markers suggest their potential for response assessment, but further research is needed to clarify their clinical applicability.

Multiparametric quantitative magnetic resonance imaging of uterine fibroids for prediction of growth rate-a pilot study.

Uterine fibroid (UF) growth rate and future morbidity cannot be predicted. This can lead to sub-optimal clinical management, with women being lost to follow-up and later presenting with severe disease that may require hospitalization, transfusions, and urgent surgical interventions. Multi-parametric quantitative magnetic resonance imaging (MRI) could provide a biomarker to predict growth rate facilitating better-informed disease management and better clinical outcomes. We assessed the ability of putative quantitative and qualitative MRI predictive factors to predict UF growth rate. Twenty women with UFs were recruited and completed baseline and follow-up MRI exams, 1-2.5 years apart. The subjects filled out symptom severity and health-related quality of life questionnaires at each visit. A standard clinical pelvic MRI non-contrast exam was performed at each visit, followed by a contrast-enhanced multi-parametric quantitative MRI (mp-qMRI) exam with T2, T2*, and apparent diffusion coefficient (ADC) mapping and dynamic contrast-enhanced MRI. Up to 3 largest fibroids were identified and outlined on the T2-weighted sequence. Fibroid morphology and enhancement patterns were qualitatively assessed on dynamic contrast-enhanced MRI. The UFs' volumes and average T2, T2*, and ADC values were calculated. Pearson correlation coefficients were calculated between UF growth rate and T2, T2*, ADC, and baseline volume. Multiple logistic regression and receiver operating characteristic (ROC) analysis were performed to predict fast-growing UFs using combinations of up to 2 significant predictors. A significance level of alpha =0.05 was used. Forty-four fibroids in 20 women had growth rate measurement available, and 36 fibroids in 16 women had follow-up quantitative MRI available. The distribution of fibroid growth rate was skewed, with approximately 20% of the fibroids exhibiting fast growth (>10 cc/year). However, there were no significant changes in median baseline and follow-up values of symptom severity and health-related quality of life scores. There was no change in average T2, T2*, and ADC at follow-up exams and there was a moderate to strong correlation to the fibroid growth rate in baseline volume and average T2 and ADC in slow-growing fibroids (<10 cc/year). A multiple logistic regression to identify fast growing UFs (>10 cc/year) achieved an area under the curve (AUC) of 0.80 with specificity of 69% at 100% sensitivity. The mp-qMRI parameters T2, ADC, and UF volume obtained at the time of initial fibroid diagnosis may be able to predict UF growth rate. Mp-qMRI could be integrated into the management of UFs, for individualized care and improved clinical outcomes.

Intravenous iron therapy results in rapid and sustained rise in myocardial iron content through a novel pathway.

Intravenous iron therapies contain iron-carbohydrate complexes, designed to ensure iron becomes bioavailable via the intermediary of spleen and liver reticuloendothelial macrophages. How other tissues obtain and handle this iron remains unknown. This study addresses this question in the context of the heart. A prospective observational study was conducted in 12 patients receiving ferric carboxymaltose (FCM) for iron deficiency. Myocardial, spleen, and liver magnetic resonance relaxation times and plasma iron markers were collected longitudinally. To examine the handling of iron taken up by the myocardium, intracellular labile iron pool (LIP) was imaged in FCM-treated mice and cells. In patients, myocardial relaxation time T1 dropped maximally 3 h post-FCM, remaining low 42 days later, while splenic T1 dropped maximally at 14 days, recovering by 42 days. In plasma, non-transferrin-bound iron (NTBI) peaked at 3 h, while ferritin peaked at 14 days. Changes in liver T1 diverged among patients. In mice, myocardial LIP rose 1 h and remained elevated 42 days after FCM. In cardiomyocytes, FCM exposure raised LIP rapidly. This was prevented by inhibitors of NTBI transporters T-type and L-type calcium channels and divalent metal transporter 1. Intravenous iron therapy with FCM delivers iron to the myocardium rapidly through NTBI transporters, independently of reticuloendothelial macrophages. This iron remains labile for weeks, reflecting the myocardium's limited iron storage capacity. These findings challenge current notions of how the heart obtains iron from these therapies and highlight the potential for long-term dosing to cause cumulative iron build-up in the heart.

Metabolite T2 relaxation times decrease across the adult lifespan in a large multi-site cohort.

Relaxation correction is crucial for accurately estimating metabolite concentrations measured using in vivo magnetic resonance spectroscopy (MRS). However, the majority of MRS quantification routines assume that relaxation values remain constant across the lifespan, despite prior evidence of T2 changes with aging for multiple of the major metabolites. Here, we comprehensively investigate correlations between T2 and age in a large, multi-site cohort. We recruited approximately 10 male and 10 female participants from each decade of life: 18-29, 30-39, 40-49, 50-59, and 60+ years old (n=101 total). We collected PRESS data at 8 TEs (30, 50, 74, 101, 135, 179, 241, and 350 ms) from voxels placed in white-matter-rich centrum semiovale (CSO) and gray-matter-rich posterior cingulate cortex (PCC). We quantified metabolite amplitudes using Osprey and fit exponential decay curves to estimate T2. Older age was correlated with shorter T2 for tNAA, tCr3.0, tCr3.9, tCho, Glx, and tissue water in CSO and PCC; rs = -0.21 to -0.65, all p<0.05, FDR-corrected for multiple comparisons. These associations remained statistically significant when controlling for cortical atrophy. T2 values did not differ across the adult lifespan for mI. By region, T2 values were longer in the CSO for tNAA, tCr3.0, tCr3.9, Glx, and tissue water and longer in the PCC for tCho and mI. These findings underscore the importance of considering metabolite T2 changes with aging in MRS quantification. We suggest that future 3T work utilize the equations presented here to estimate age-specific T2 values instead of relying on uniform default values.