Fully automated planning for anatomical fetal brain MRI on 0.55T.

PURPOSE: Widening the availability of fetal MRI with fully automatic real-time planning of radiological brain planes on 0.55T MRI. METHODS: Deep learning-based detection of key brain landmarks on a whole-uterus echo planar imaging scan enables the subsequent fully automatic planning of the radiological single-shot Turbo Spin Echo acquisitions. The landmark detection pipeline was trained on over 120 datasets from varying field strength, echo times, and resolutions and quantitatively evaluated. The entire automatic planning solution was tested prospectively in nine fetal subjects between 20 and 37 weeks. A comprehensive evaluation of all steps, the distance between manual and automatic landmarks, the planning quality, and the resulting image quality was conducted. RESULTS: Prospective automatic planning was performed in real-time without latency in all subjects. The landmark detection accuracy was 4.2 ± $$ \pm $$ 2.6 mm for the fetal eyes and 6.5 ± $$ \pm $$ 3.2 for the cerebellum, planning quality was 2.4/3 (compared to 2.6/3 for manual planning) and diagnostic image quality was 2.2 compared to 2.1 for manual planning. CONCLUSIONS: Real-time automatic planning of all three key fetal brain planes was successfully achieved and will pave the way toward simplifying the acquisition of fetal MRI thereby widening the availability of this modality in nonspecialist centers.

Pore size estimation in axon-mimicking microfibers with diffusion-relaxation MRI.

PURPOSE: This study aims to evaluate two distinct approaches for fiber radius estimation using diffusion-relaxation MRI data acquired in biomimetic microfiber phantoms that mimic hollow axons. The methods considered are the spherical mean power-law approach and a T2-based pore size estimation technique. THEORY AND METHODS: A general diffusion-relaxation theoretical model for the spherical mean signal from water molecules within a distribution of cylinders with varying radii was introduced, encompassing the evaluated models as particular cases. Additionally, a new numerical approach was presented for estimating effective radii (i.e., MRI-visible mean radii) from the ground truth radii distributions, not reliant on previous theoretical approximations and adaptable to various acquisition sequences. The ground truth radii were obtained from scanning electron microscope images. RESULTS: Both methods show a linear relationship between effective radii estimated from MRI data and ground-truth radii distributions, although some discrepancies were observed. The spherical mean power-law method overestimated fiber radii. Conversely, the T2-based method exhibited higher sensitivity to smaller fiber radii, but faced limitations in accurately estimating the radius in one particular phantom, possibly because of material-specific relaxation changes. CONCLUSION: The study demonstrates the feasibility of both techniques to predict pore sizes of hollow microfibers. The T2-based technique, unlike the spherical mean power-law method, does not demand ultra-high diffusion gradients, but requires calibration with known radius distributions. This research contributes to the ongoing development and evaluation of neuroimaging techniques for fiber radius estimation, highlights the advantages and limitations of both methods, and provides datasets for reproducible research.

Very-long T2-weighted imaging of the non-lesional brain tissue in multiple sclerosis patients.

The purpose of this study is to demonstrate that T2-weighted imaging with very long echo time (TE > 300 ms) can provide relevant information in neurodegenerative/inflammatory disorder. Twenty patients affected by relapsing-remitting multiple sclerosis with stable disease course underwent 1.5 T 3D FLAIR, 3D T1-weighted, and a multi-echo sequence with 32 echoes (TE = 10-320 ms). Focal lesions (FL) were identified on FLAIR. T1-images were processed to segment deep gray matter (dGM), white matter (WM), FL sub-volumes with T1 hypo-intensity (T1FL), and dGM volumes (atrophy). Clinical-radiological parameters included Expanded Disability Status Scale (EDSS), disease duration, patient age, T1FL, and dGM atrophy. Correlation analysis was performed between the mean signal intensity (SI) computed on the non-lesional dGM and WM at different TE versus the clinical-radiological parameters. Multivariable linear regressions were fitted to the data to assess the association between the dependent variable EDSS and the independent variables obtained by T1FL lesion load and the mean SI of dGM and WM at the different TE. A clear trend is observed, with a systematic strengthening of the significance of the correlation at longer TE for all the relationships with the clinical-radiological parameters, becoming significant (p < 0.05) for EDSS, T1FL volumes, and dGM atrophy. Multivariable linear regressions show that at shorter TE, the SI of the T2-weighted sequences is not relevant for describing the EDSS variability while the T1FL volumes are relevant, and vice versa, at very-long TEs (around 300 ms); the SI of the T2-weighted sequences significantly (p < 0.05) describes the EDSS variability. By very long TE, the SI primarily originates from water with a T2 longer than 250 ms and/or free water, which may be arising from the perivascular space (PVS). Very-long T2-weighting might detect dilated PVS and represent an unexplored MR approach in neurofluid imaging of neurodegenerative/inflammatory diseases.

T2*-Relaxometry MRI to Assess Third Trimester Placental and Fetal Brain Oxygenation and Placental Characteristics in Healthy Fetuses and Fetuses With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) has been linked to impaired placental and fetal brain development. Assessing the placenta and fetal brain in parallel may help further our understanding of the relationship between development of these organs. HYPOTHESIS: 1) Placental and fetal brain oxygenation are correlated, 2) oxygenation in these organs is reduced in CHD compared to healthy controls, and 3) placental structure is altered in CHD. STUDY TYPE: Retrospective case-control. POPULATION: Fifty-one human fetuses with CHD (32 male; median [IQR] gestational age [GA] = 32.0 [30.9-32.9] weeks) and 30 from uncomplicated pregnancies with normal birth outcomes (18 male; median [IQR] GA = 34.5 [31.9-36.7] weeks). FIELD STRENGTH/SEQUENCE: 1.5 T single-shot multi-echo-gradient-echo echo-planar imaging. ASSESSMENT: Masking was performed using an automated nnUnet model. Mean brain and placental T2* and quantitative measures of placental texture, volume, and morphology were calculated. STATISTICAL TESTS: Spearman's correlation coefficient for determining the association between brain and placental T2*, and between brain and placental characteristics with GA. P-values for comparing brain T2*, placenta T2*, and placental characteristics between groups derived from ANOVA. Significance level P < 0.05. RESULTS: There was a significant positive association between placental and fetal brain T2* (⍴ = 0.46). Placental and fetal brain T2* showed a significant negative correlation with GA (placental T2* ⍴ = -0.65; fetal brain T2* ⍴ = -0.32). Both placental and fetal brain T2* values were significantly reduced in CHD, after adjusting for GA (placental T2*: control = 97 [±24] msec, CHD = 83 [±23] msec; brain T2*: control = 218 [±26] msec, CHD = 202 [±25] msec). Placental texture and morphology were also significantly altered in CHD (Texture: control = 0.84 [0.83-0.87], CHD = 0.80 [0.78-0.84]; Morphology: control = 9.9 [±2.2], CHD = 10.8 [±2.0]). For all fetuses, there was a significant positive association between placental T2* and placental texture (⍴ = 0.46). CONCLUSION: Placental and fetal brain T2* values are associated in healthy fetuses and those with CHD. Placental and fetal brain oxygenation are reduced in CHD. Placental appearance is significantly altered in CHD and shows associations with placental oxygenation, suggesting altered placental development and function may be related. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Real-time fetal brain tracking for functional fetal MRI.

PURPOSE: To improve motion robustness of functional fetal MRI scans by developing an intrinsic real-time motion correction method. MRI provides an ideal tool to characterize fetal brain development and growth. It is, however, a relatively slow imaging technique and therefore extremely susceptible to subject motion, particularly in functional MRI experiments acquiring multiple Echo-Planar-Imaging-based repetitions, for example, diffusion MRI or blood-oxygen-level-dependency MRI. METHODS: A 3D UNet was trained on 125 fetal datasets to track the fetal brain position in each repetition of the scan in real time. This tracking, inserted into a Gadgetron pipeline on a clinical scanner, allows updating the position of the field of view in a modified echo-planar imaging sequence. The method was evaluated in real-time in controlled-motion phantom experiments and ten fetal MR studies (17 + 4-34 + 3 gestational weeks) at 3T. The localization network was additionally tested retrospectively on 29 low-field (0.55T) datasets. RESULTS: Our method achieved real-time fetal head tracking and prospective correction of the acquisition geometry. Localization performance achieved Dice scores of 84.4% and 82.3%, respectively for both the unseen 1.5T/3T and 0.55T fetal data, with values higher for cephalic fetuses and increasing with gestational age. CONCLUSIONS: Our technique was able to follow the fetal brain even for fetuses under 18 weeks GA in real-time at 3T and was successfully applied "offline" to new cohorts on 0.55T. Next, it will be deployed to other modalities such as fetal diffusion MRI and to cohorts of pregnant participants diagnosed with pregnancy complications, for example, pre-eclampsia and congenital heart disease.

MRI Deep Learning-Based Automatic Segmentation of Interventricular Septum for Black-Blood Myocardial T2* Measurement in Thalassemia.

BACKGROUND: The T2* value of interventricular septum is routinely reported for grading myocardial iron load in thalassemia major, and automatic segmentation of septum could shorten analysis time and reduce interobserver variability. PURPOSE: To develop a deep learning-based method for automatic septum segmentation from black-blood MR images for the myocardial T2* measurement of thalassemia patients. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: One hundred forty-six transfusion-dependent thalassemia patients with cardiac MR examinations from two centers. Data from Center 1 (1.5 T) were assigned to the training (100 examinations) and internal testing (20 examinations) sets; data from Center 2 were assigned to the external testing set (26 examinations; 10 at 1.5 T and 16 at 3.0 T). FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T, multiecho gradient-echo sequence. ASSESSMENT: A modified attention U-Net for septum segmentation was constructed and trained, and its performance evaluated on unseen internal and external datasets. T2* was measured by fitting the average septum signal, separately segmented by automatic and manual methods. STATISTICAL TESTS: Agreement between manual and automatic septum segmentations was assessed with the Dice coefficient, and T2* agreement was assessed using the Bland-Altman plot and the coefficient of variation (CoV). RESULTS: The median Dice coefficient of deep network-based septum segmentation was 0.90 [0.05] on the internal dataset, 0.82 [0.10] on the external 1.5 T dataset, and 0.86 [0.14] on the external 3.0 T dataset. T2* measurements using automatic segmentation corresponded with those from manual segmentation, with a mean difference of 0.02 (95% LoA: -0.74 to 0.79) msec, 0.43 (95% LoA: -2.1 to 3.0) msec, and 0.36 (95% LoA: -0.72 to 1.4) msec on the three datasets. The CoVs between the two methods were 3.1%, 7.0%, and 6.1% on the internal and two external datasets, respectively. DATA CONCLUSIONS: The proposed septum segmentation yielded myocardial T2* measurements which were highly consistent with those obtained by manual segmentation. This automatic approach may facilitate data processing and avoid operator-dependent variability in practice. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 1.

New Insights into the Spread of MRS-Based Water T2 Values Observed in Highly Fatty Replaced Muscles.

BACKGROUND: The reference standard for assessing water T2 (T2,H2O ) at high fat fraction (FF) is 1 H MRS. T2,H2O (T2,H2O,MRS ) dependence on FF (FFMRS ) has recently been demonstrated in muscle at high FF (i.e. ≥60%). PURPOSE: To investigate the relationship between T2,H2O,MRS and FFMRS in the thigh/leg muscles of patients with neuromuscular diseases and to compare with quantitative MRI. STUDY TYPE: Retrospective case-control study. POPULATION: A total of 151 patients with neuromuscular disorders (mean age ± standard deviation = 52.5 ± 22.6 years, 54% male), 44 healthy volunteers (26.5 ± 13.0 years, 57% male). FIELD STRENGTH/SEQUENCE: A 3-T; single-voxel stimulated echo acquisition mode (STEAM) MRS, multispin echo (MSE) imaging (for T2 mapping, T2,H2O,MRI ), three-point Dixon imaging (for FFMRI and R 2 * mapping). ASSESSMENT: Mono-exponential and bi-exponential models were fitted to water T2 decay curves to extract T2,H2O,MRS and FFMRS . Water resonance full-width-at-half-maximum (FWHM) and B0 spread (∆B0 ) values were calculated. T2,H2O,MRI (mean), FFMRI (mean, kurtosis, and skewness), and R 2 * (mean) values were estimated in the MRS voxel. STATISTICAL TESTS: Mann-Whitney U tests, Kruskal-Wallis tests. A P-value <0.05 was considered statistically significant. RESULTS: Normal T2,H2O,MRS threshold was defined as the 90th percentile in healthy controls: 30.3 msec. T2,H2O,MRS was significantly higher in all patients with FFMRS < 60% compared to healthy controls. We discovered two subgroups in patients with FFMRS ≥ 60%: one with T2,H2O,MRS ≥ 30.3 msec and one with T2,H2O,MRS < 30.3 msec including abnormally low T2,H2O,MRS . The latter subgroup had significantly higher water resonance FWHM, ∆B0 , FFMRI kurtosis, and skewness values but nonsignificantly different R 2 * (P = 1.00) and long T2,H2O,MRS component and its fraction (P > 0.11) based on the bi-exponential analysis. DATA CONCLUSION: The findings suggest that the cause for (abnormally) T2,H2O,MRS at high FFMRS is biophysical, due to differences in susceptibility between muscle and fat (increased FWHM and ∆B0 ), rather than pathophysiological such as compartmentation changes, which would be reflected by the bi-exponential analysis. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Peripheral nerve involvement in hereditary spastic paraplegia characterized by quantitative magnetic resonance neurography.

BACKGROUND AND OBJECTIVES: Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders. While peripheral nerve involvement is frequent in spastic paraplegia 7 (SPG7), the evidence of peripheral nerve involvement in SPG4 is more controversial. We aimed to characterize lower extremity peripheral nerve involvement in SPG4 and SPG7 by quantitative magnetic resonance neurography (MRN). METHODS: Twenty-six HSP patients carrying either the SPG4 or SPG7 mutation and 26 age-/sex-matched healthy controls prospectively underwent high-resolution MRN with large coverage of the sciatic and tibial nerve. Dual-echo turbo-spin-echo sequences with spectral fat-saturation were utilized for T2-relaxometry and morphometric quantification, while two gradient-echo sequences with and without an off-resonance saturation rapid frequency pulse were applied for magnetization transfer contrast (MTC) imaging. HSP patients additionally underwent detailed neurologic and electroneurographic assessments. RESULTS: All microstructural (proton spin density [ρ], T2-relaxation time, magnetization transfer ratio) and morphometric (cross-sectional area) quantitative MRN markers were decreased in SPG4 and SPG7 indicating chronic axonopathy. ρ was superior in differentiating subgroups and identifying subclinical nerve damage in SPG4 and SPG7 without neurophysiologic signs of polyneuropathy. MRN markers correlated well with clinical scores and electroneurographic results. CONCLUSIONS: MRN characterizes peripheral nerve involvement in SPG4 and SPG7 as a neuropathy with predominant axonal loss. Evidence of peripheral nerve involvement in SPG4 and SPG7, even without electroneurographically manifest polyneuropathy, and the good correlation of MRN markers with clinical measures of disease progression, challenge the traditional view of the existence of HSPs with isolated pyramidal signs and suggest MRN markers as potential progression biomarkers in HSP.

Separating spin compartments in arterial spin labeling using delays alternating with nutation for tailored excitation (DANTE) pulse: A validation study using T2 -relaxometry and application to arterial cerebral blood volume imaging.

PURPOSE: To clarify the type of spin compartment in arterial spin labeling (ASL) that is eliminated by delays alternating with nutation for tailored excitation (DANTE) pulse using T2 -relaxometry, and to demonstrate the feasibility of arterial cerebral blood volume (CBVa ) imaging using DANTE-ASL in combination with a simplified two-compartment model. METHOD: The DANTE and T2 -preparation modules were combined into a single ASL sequence. T2 values under the application of DANTE were determined to evaluate changes in T2 , along with the post-labeling delay (PLD) and the relationship between transit time without DANTE (TTnoVS ) and T2 . The reference tissue T2 (T2_ref ) was also obtained. Subsequently, the DANTE module was embedded into the Hadamard-encoded ASL. Cerebral blood flow (CBF) and CBVa were computed using two Hadamard-encoding datasets (with and without DANTE) in a rest and breath-holding (BH) task. RESULTS: While T2 without DANTE (T2_noVS ) decreased as the PLD increased, T2 with DANTE (T2_DANTE ) was equivalent to T2_ref and did not change with the PLD. Although there was a significant positive correlation between TTnoVS and T2_noVS with short PLD, T2_DANTE was not correlated with TTnoVS nor PLD. Baseline CBVa values obtained at rest were 0.64 ± 0.12, 0.64 ± 0.11, and 0.58 ± 0.15 mL/100 g for anterior, middle, and posterior cerebral arteries, respectively. Significant CBF and CBVa elevations were observed in the BH task. CONCLUSION: Microvascular compartment signals were eliminated from the total ASL signals by DANTE. CBVa can be measured using Hadamard-encoded DANTE-ASL in combination with a simplified two-compartment model.

Liver iron quantification in children and young adults: comparison of a volumetric multi-echo 3-D Dixon sequence with conventional 2-D T2* relaxometry.

BACKGROUND: Magnetic resonance imaging (MRI)-based liver iron quantification is the standard of care to guide chelation therapy in children at risk of hemochromatosis. T2* relaxometry is the most widely used technique but requires third-party software for post-processing. Vendor-provided three-dimensional (3-D) multi-echo Dixon techniques are now available that allow inline/automated post-processing. OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of a volumetric multi-echo Dixon technique using conventional T2* relaxometry as the reference standard in a pediatric and young adult population. MATERIALS AND METHODS: In this retrospective study, we queried the radiology information system to identify all MRIs performed for liver iron quantification from July 2015 to January 2020. All patients had undergone T2* relaxometry on a 1.5-tesla (T) scanner for liver iron concentration (LIC) estimation. In addition, a 3-D multi-echo Dixon was performed using Siemens Healthineers LiverLab (Erlangen, Germany). Two readers independently estimated liver R2* and T2* on the multi-echo Dixon by drawing free-hand regions of interest on the scanner-generated R2* and T2* maps. Conventional T2*-relaxometry-based LIC was the reference standard. We estimated interobserver agreement by concordance correlation coefficient (CCC). We used Bland-Altman analysis and Pearson correlation coefficient (r) to compare LIC by the two methods. RESULTS: Fifty-four MRIs on 38 patients (22 females) were available for analysis. Mean patient age was 11.8 years (standard deviation [SD] 5.3 years). Reference standard LIC ranged 1.1-21.1 (median 6.8) mg/g dry weight of liver. The concordance between readers for T2* estimation using 3-D multi-echo Dixon was substantial (CCC 0.99, confidence interval 0.99-1.00). Bland-Altman plot showed that all observations were clustered around the zero bias line if the LIC average was ≤8 mg/g, and r was very strong (reader 1 r=0.93, reader 2 r=0.92, both P-values <0.001). With increasing LIC, there was a pattern of poor agreement on the Bland-Altman plot, with observations crossing the lower limits of agreement, and r was very weak (reader 1 r=0.05, P-value 0.84; reader 2 r=0.17, P-value 0.44). CONCLUSION: Vendor-based 3-D multi-echo Dixon allows for excellent interobserver correlation in liver T2* estimation. LIC estimated by this method has a very strong correlation with conventional T2* relaxometry if liver iron overload is mild-moderate (LIC ≤8 mg/g).

An MRI approach to assess placental function in healthy humans and sheep.

KEY POINTS: Human placental function is evaluated using non-invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption ( VO2 ) is only possible during Caesarean delivery. This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and VO2 by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental VO2 by MRI was ∼4 ml min-1  kg-1 fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques. Our MRI approach can quantify uteroplacental VO2 , which involves the quantification of maternal- and fetal-placental blood flows, fetal oxygen delivery and VO2 , and the oxygen gradient between uterine- and umbilical-venous blood, providing a comprehensive assessment of placental function with clinical potential. ABSTRACT: It has not been feasible to perform routine clinical measurement of human placental oxygen consumption ( VO2 ) and in vitro studies do not reflect true metabolism in utero. Here we propose an MRI method to non-invasively quantify in utero placental and fetal oxygen delivery ( DO2 ) and VO2 in healthy humans and sheep. Women (n = 20) and Merino sheep (n = 10; 23 sets of measurements) with singleton pregnancies underwent an MRI in late gestation (36 ± 2 weeks and 128 ± 9 days, respectively; mean ± SD). Blood flow (phase-contrast) and oxygen content (T1 and T2 relaxometry) were measured in the major uterine- and umbilical-placental vessels, allowing calculation of uteroplacental and fetal DO2 and VO2 . Maternal DO2 (ml min-1  kg-1 fetus) to the gravid uterus was similar in humans and sheep (human = 54 ± 15, sheep = 53 ± 21, P = 0.854), while fetal DO2 (human = 25 ± 4, sheep = 22 ± 5, P = 0.049) was slightly lower in sheep. Uteroplacental and fetal VO2 (ml min-1  kg-1 fetus; uteroplacental: human = 4.1 ± 1.5, sheep = 3.5 ± 1.9, P = 0.281; fetus: human = 6.8 ± 1.3, sheep = 7.2 ± 1.7, P = 0.426) were similar between species. Late gestational uteroplacental:fetal VO2 ratio did not change with age (human, P = 0.256; sheep, P = 0.121). Human umbilical blood flow (ml min-1  kg-1 fetus) decreased with advancing age (P = 0.008), while fetal VO2 was preserved through an increase in oxygen extraction (P = 0.046). By contrast, sheep fetal VO2 was preserved through stable umbilical flow (ml min-1  kg-1 ; P = 0.443) and oxygen extraction (P = 0.582). MRI derived measurements of uteroplacental and fetal VO2 between humans and sheep were similar and in keeping with prior data obtained using invasive techniques. Taken together, these data confirm the reliability of our approach, which offers a novel clinical 'placental function test'.

Resolving bundle-specific intra-axonal T2 values within a voxel using diffusion-relaxation tract-based estimation.

At the typical spatial resolution of MRI in the human brain, approximately 60-90% of voxels contain multiple fiber populations. Quantifying microstructural properties of distinct fiber populations within a voxel is therefore challenging but necessary. While progress has been made for diffusion and T1-relaxation properties, how to resolve intra-voxel T2 heterogeneity remains an open question. Here a novel framework, named COMMIT-T2, is proposed that uses tractography-based spatial regularization with diffusion-relaxometry data to estimate multiple intra-axonal T2 values within a voxel. Unlike previously-proposed voxel-based T2 estimation methods, which (when applied in white matter) implicitly assume just one fiber bundle in the voxel or the same T2 for all bundles in the voxel, COMMIT-T2 can recover specific T2 values for each unique fiber population passing through the voxel. In this approach, the number of recovered unique T2 values is not determined by a number of model parameters set a priori, but rather by the number of tractography-reconstructed streamlines passing through the voxel. Proof-of-concept is provided in silico and in vivo, including a demonstration that distinct tract-specific T2 profiles can be recovered even in the three-way crossing of the corpus callosum, arcuate fasciculus, and corticospinal tract. We demonstrate the favourable performance of COMMIT-T2 compared to that of voxelwise approaches for mapping intra-axonal T2 exploiting diffusion, including a direction-averaged method and AMICO-T2, a new extension to the previously-proposed Accelerated Microstructure Imaging via Convex Optimization (AMICO) framework.

T2 heterogeneity as an in vivo marker of microstructural integrity in medial temporal lobe subfields in ageing and mild cognitive impairment.

A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n = 49) compared to healthy older controls (n = 99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in CA1-3 and entorhinal cortex and volume of entorhinal cortex showed some ability to predict cognitive decline, where absolute T2 could not, however further studies are required to verify this result. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative diseases and the study of brain-behaviour relationships.

Association Between T2* Relaxation Times Derived From Ultrashort Echo Time MRI and Symptoms During Exercise Therapy for Patellar Tendinopathy: A Large Prospective Study.

BACKGROUND: Exercise therapy is considered preferential treatment for patellar tendinopathy (PT). However, there is conflicting evidence for structural patellar tendon adaptation in response to exercise therapy and its association with symptoms is weak. PURPOSE: To assess the association between 1) T2* relaxation times and symptom severity; 2) baseline T2* and clinical outcome; and 3) longitudinal T2* changes and clinical outcome in athletes with PT performing exercise therapy. STUDY TYPE: Randomized controlled clinical trial. SUBJECTS: Seventy-six athletes (18-35 years) with clinically diagnosed and ultrasound-confirmed PT. FIELD STRENGTH/SEQUENCE: 3D gradient echo sequence (3.0 T). ASSESSMENT: Patients were enrolled in a randomized trial of progressive tendon-loading exercises (PTLE) versus eccentric exercise therapy (EET). Symptoms were assessed using the Victorian Institute of Sports Assessment (VISA-P) questionnaire. 3D-Ultrashort echo time (UTE)-MRI was acquired at baseline, 12 and 24 weeks. Voxel-wise T2* relaxation times were quantified using mono-exponential and bi-exponential models. T2* analysis was performed in three patellar tendon tissue compartments representing: aligned collagen, degenerative tissue, and interface. STATISTICAL TESTS: Adjusted general linear, mixed-linear models, and generalized estimating equations. RESULTS: We included 76 patients with PT (58 men, mean age 24 ± 4 years); 38 in the PTLE-group and 38 in the EET-group, of which 57 subjects remained eligible for analysis. T2* relaxation times were significantly associated with VISA-P in degenerative and interface tissues of the patellar tendon. No association was found between baseline T2* and VISA-P after 24 weeks (P > 0.29). The estimated mean T2* in degenerative tissue decreased from 14 msec (95%CI: 12-16) at baseline to 13 msec (95%CI: 11-15) at 12 weeks and to 13 msec (95%CI: 10-15) at 24 weeks. The significant decrease in T2* from baseline to 24 weeks was associated with improved clinical outcome. DATA CONCLUSION: Tissue-specific T2* relaxation times, identified with 3D-UTE-MRI, decreased significantly in athletes with patellar tendinopathy performing exercise therapy and this decrease was associated with improved clinical outcome. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

T2 Relaxometry Evidence of Microstructural Changes in Diffusely Abnormal White Matter in Relapsing-Remitting Multiple Sclerosis and Clinically Isolated Syndrome: Impact on Visuomotor Performance.

BACKGROUND: Although diffusely abnormal white matter (DAWM) is commonly seen in multiple sclerosis (MS), it is rarely considered in clinical/imaging studies. PURPOSE: To evaluate quantitative markers of microstructural changes in DAWM of patients with clinically isolated syndrome (CIS) and relapsing-remitting MS (RR-MS) in relation to MS lesions and degree of neurocognitive impairment, by using a multi-echo spin echo (MESE) Proton Density PD-to-T2 sequence. STUDY TYPE: Prospective, cross-sectional. POPULATION: Thirty-seven RR-MS patients, 33 CIS patients, and 52 healthy controls. FIELD STRENGTH/SEQUENCE: 1.5 T/T1-, T2-weighted, fluid-attenuated inversion recovery, and MESE sequences. ASSESSMENT: Long T2, short T2, and myelin water fraction (MWF) values were estimated as indices of intra/extracellular water content and myelin content, respectively, in DAWM, posterior periventricular normal appearing white matter (NAWM), and focal MS lesions, classified according to their signal intensity on T1 sequences. Patients were, also, administered a battery of neuropsychological tests. STATISTICAL TESTS: Comparisons of T2 and MWF values in DAWM, NAWM, and MS lesions were examined, using two-way mixed analyses of variance. Associations of Grooved Pegboard performance with T2 and MWF values in DAWM and NAWM were assessed using Pearson correlation coefficients. RESULTS: T2 and MWF values of DAWM were intermediate between the respective values of NAWM and T1 hypointense focal lesions, while there was no difference between the respective values of DAWM and T1-isointense lesions. T2 values in DAWM were strongly associated with visuomotor performance in CIS patients. DATA CONCLUSION: Intra/extracellular water and myelin water content of DAWM are similar to those of T1-isointense lesions and predict visuomotor performance in CIS patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Multiexponential Analysis of the Water T2-Relaxation in the Skeletal Muscle Provides Distinct Markers of Disease Activity Between Inflammatory and Dystrophic Myopathies.

BACKGROUND: The monoexponential water T2 (T2-mono ) is a proven biomarker of disease activity in neuromuscular disorders (NMDs). However, it lacks specificity, being elevated in the presence of several pathological processes and pathomorphological alterations in the muscle tissue. PURPOSE: To investigate the multiexponential behavior of the water T2 -relaxation in the skeletal muscle of NMD patients, aiming to identify more sensitive and specific biomarkers of disease activity. STUDY TYPE: Retrospective case-control. POPULATION: Thirty Duchenne muscular dystrophy and 114 inclusion body myositis patients and 55 control subjects. FIELD STRENGTH/SEQUENCE: 3T/Single-voxel proton spectroscopy (1 H-MRS) and multispin-echo (MSE) imaging. ASSESSMENT: Water T2 -decay curves generated from 1 H-MRS data acquired at 14 echo-times were fitted to mono- and biexponential models and the adjusted R2 of each fit was computed. Additionally, T2 spectra were generated from a regularized inverse Laplace transform. For comparison, water T2 maps were generated from the MSE data. The performances of the different variables at identifying patients were assessed via receiver operating characteristic (ROC)-curve analysis. STATISTICAL TESTS: Chi-square, Kruskal-Wallis, and Mann-Whitney with Bonferroni correction for multiple comparisons. RESULTS: T2-mono was elevated in patients (P<0.05), but could not distinguish inclusion body myositis (IBM) from Duchenne muscular dystrophy (DMD). While 79% of IBM data presented a biexponential behavior, this was only 16% and 10% for DMD and control data, respectively (P<0.05). All T2 spectra presented an intermediate-T2 peak characterized by an elevated T2 in patients (P<0.05) and by a relative fraction that was abnormally smaller in IBM patients (P<0.05). Also, a long-T2 peak was exclusively observed in IBM patients. A combination of T2 -spectrum variables performed best at identifying patients. DATA CONCLUSION: T2 spectra not only provided more sensitive and specific markers of disease presence than the T2-mono , but also allowed distinguishing IBM from DMD patients. This must reflect distinct predominant pathological alterations between these diseases, suggesting that these markers provide additional pathophysiological/histopathological information that are missing from T2-mono . LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Quantitative muscle MRI as a sensitive marker of early muscle pathology in myotonic dystrophy type 1.

BACKGROUND: Quantitative muscle MRI as a sensitive marker of early muscle pathology and disease progression in adult-onset myotonic dystrophy type 1. The utility of muscle MRI as a marker of muscle pathology and disease progression in adult-onset myotonic dystrophy type 1 (DM1) was evaluated. METHODS: This prospective, longitudinal study included 67 observations from 36 DM1 patients (50% female), and 92 observations from 49 healthy adults (49% female). Lower-leg 3T magnetic resonance imaging (MRI) scans were acquired. Volume and fat fraction (FF) were estimated using a three-point Dixon method, and T2-relaxometry was determined using a multi-echo spin-echo sequence. Muscles were segmented automatically. Mixed linear models were conducted to determine group differences across muscles and image modality, accounting for age, sex, and repeated observations. Differences in rate of change in volume, T2-relaxometry, and FF were also determined with mixed linear regression that included a group by elapsed time interaction. RESULTS: Compared with healthy adults, DM1 patients exhibited reduced volume of the tibialis anterior, soleus, and gastrocnemius (GAS) (all, P < .05). T2-relaxometry and FF were increased across all calf muscles in DM1 compared to controls. (all, P < .01). Signs of muscle pathology, including reduced volume, and increased T2-relaxometry and FF were already noted in DM1 patients who did not exhibit clinical motor symptoms of DM1. As a group, DM1 patients exhibited a more rapid change than did controls in tibialis posterior volume (P = .05) and GAS T2-relaxometry (P = .03) and FF (P = .06). CONCLUSIONS: Muscle MRI renders sensitive, early markers of muscle pathology and disease progression in DM1. T2 relaxometry may be particularly sensitive to early muscle changes related to DM1.

Comparison of T2 relaxometry and PET CT in the evaluation of patients with mesial temporal lobe epilepsy using video EEG as the reference standard.

PURPOSE: Our study aimed to compare the sensitivity of T2 relaxometry and positron emission tomography - computed tomography (PET/CT) in patients with a history suggestive of mesial temporal lobe epilepsy using video electroencephalography (EEG) as the reference standard. MATERIAL AND METHODS: In our study, 35 patients with a history suggestive of mesial temporal lobe epilepsy were subjected to conventional magnetic resonance imaging (MRI), T2 relaxometry, and PET/CT. The results of each of the studies were compared with video EEG findings. Analyses were performed by using statistical software (SPSS version 20.0 for windows), and the sensitivity of conventional MRI, T2 relaxometry, and PET/CT were calculated. RESULTS: The sensitivity of qualitative MRI (atrophy and T2 hyperintensity), quantitative MRI (T2 relaxometry), and PET/CT in lateralizing the seizure focus were 68.6% (n = 24), 85.7% (n = 30), and 88.6% (n = 31), respectively. CONCLUSIONS: The sensitivity of MRI in lateralization and localization of seizure focus in temporal lobe epilepsy can be increased by adding the quantitative parameter (T2 relaxometry) with the conventional sequences. T2 Relaxometry is comparable to PET/CT for localization and lateralization of seizure focus and is a useful tool in the workup of TLE patients.

Myelin water imaging from multi-echo T2 MR relaxometry data using a joint sparsity constraint.

Demyelination is the key pathological process in multiple sclerosis (MS). The extent of demyelination can be quantified with magnetic resonance imaging by assessing the myelin water fraction (MWF). However, long computation times and high noise sensitivity hinder the translation of MWF imaging to clinical practice. In this work, we introduce a more efficient and noise robust method to determine the MWF using a joint sparsity constraint and a pre-computed B1+-T2 dictionary. A single component analysis with this dictionary is used in an initial step to obtain a B1+ map. The T2 distribution is then determined from a reduced dictionary corresponding to the estimated B1+ map using a combination of a non-negativity and a joint sparsity constraint. The non-negativity constraint ensures that a feasible solution with non-negative contribution of each T2 component is obtained. The joint sparsity constraint restricts the T2 distribution to a small set of T2 relaxation times shared between all voxels and reduces the noise sensitivity. The applied Sparsity Promoting Iterative Joint NNLS (SPIJN) algorithm can be implemented efficiently, reducing the computation time by a factor of 50 compared to the commonly used regularized non-negative least squares algorithm. The proposed method was validated in simulations and in 8 healthy subjects with a 3D multi-echo gradient- and spin echo scan at 3 â€‹T. In simulations, the absolute error in the MWF decreased from 0.031 to 0.013 compared to the regularized NNLS algorithm for SNR â€‹= â€‹250. The in vivo results were consistent with values reported in literature and improved MWF-quantification was obtained especially in the frontal white matter. The maximum standard deviation in mean MWF in different regions of interest between subjects was smaller for the proposed method (0.0193) compared to the regularized NNLS algorithm (0.0266). In conclusion, the proposed method for MWF estimation is less computationally expensive and less susceptible to noise compared to state of the art methods. These improvements might be an important step towards clinical translation of MWF measurements.

Dehydration assessment via a portable, single sided magnetic resonance sensor.

PURPOSE: Undiagnosed dehydration compromises health outcomes across many populations. Existing dehydration diagnostics require invasive bodily fluid sampling or are easily confounded by fluid and electrolyte intake, environment, and physical activity limiting widespread adoption. We present a portable MR sensor designed to measure intramuscular fluid shifts to identify volume depletion. METHODS: Fluid loss is induced via a mouse model of thermal dehydration (37°C; 15-20% relative humidity). We demonstrate quantification of fluid loss induced by hyperosmotic dehydration with multicomponent T2 relaxometry using both a benchtop NMR system and MRI localized to skeletal muscle tissue. We then describe a miniaturized (~1000 cm3 ) portable (~4 kg) MR sensor (0.28 T) designed to identify dehydration-induced fluid loss. T2 relaxometry measurements were performed using a Carr-Purcell-Meiboom-Gill pulse sequence in ~4 min. RESULTS: T2 values from the portable MR sensor exhibited strong (R2 = 0.996) agreement with benchtop NMR spectrometer. Thermal dehydration induced weight loss of 4 to 11% over 5 to 10 h. Fluid loss induced by thermal dehydration was accurately identified via whole-animal NMR and skeletal muscle. The portable MR sensor accurately identified dehydration via multicomponent T2 relaxometry. CONCLUSION: Performing multicomponent T2 relaxometry localized to the skeletal muscle with a miniaturized MR sensor provides a noninvasive, physiologically relevant measure of dehydration induced fluid loss in a mouse model. This approach offers sensor portability, reduced system complexity, fully automated operation, and low cost compared with MRI. This approach may serve as a versatile and portable point of care technique for dehydration monitoring.