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Purpose: To compare postmortem in situ with ex situ MRI parameters, including volumetry, diffusion tensor imaging (DTI), and relaxometry for assessing methodology‐induced alterations, which is a crucial prerequisite when performing MRI biomarker validation. Methods: MRI whole‐brain scans of five deceased patients with amyotrophic lateral sclerosis were performed at 3 T. In situ scans were conducted within 32 h after death (SD 18 h), and ex situ scans after brain extraction and 3 months of formalin fixation. The imaging protocol included MP2RAGE, DTI, and multi‐contrast spin‐echo and multi‐echo gradient‐echo sequences. Volumetry, fractional anisotropy, mean diffusivity, T1, T2, and T2*$$ {T}_2^{\ast } $$ have been assessed for specific brain regions. Results: When comparing ex situ to in situ values, the following results were obtained. Deep gray matter as well as the thalamus and the hippocampus showed a reduced volume. Fractional anisotropy was reduced in the cortex and the whole brain. Mean diffusivity was decreased in white matter and deep gray matter. T1 and T2 were reduced in all investigated structures, whereas T2*$$ {T}_2^{\ast } $$ was increased in the cortex. Conclusion: The results of this study show that the volumes and MRI parameters of several brain regions are potentially affected by tissue extraction and subsequent formalin fixation, suggesting that methodological alterations are present in ex situ MRI. To avoid overlap of indistinguishable methodological and disease‐related changes, we recommend performing in situ postmortem MRI as an additional intermediate step for in vivo MRI biomarker validation. [ABSTRACT FROM AUTHOR]

Purpose: To establish an interleaved multislice variant of the averaged magnetization inversion‐recovery acquisitions (AMIRA) approach for 2D spinal cord imaging with increased acquisition efficiency compared with the conventional 2D single‐slice approach(es), and to determine essential prerequisites for a working interleaved multislice AMIRA approach in practice. Methods: The general AMIRA concept is based on an inversion recovery–prepared, segmented, and time‐limited cine balanced SSFP sequence, generating images of different contrast. For AMIRA imaging of multiple, independent slices in a 2D interleaved fashion, a slice loop within the acquisition loops was programmed. The former non‐selective inversions were replaced with slice‐selective inversions with user‐definable slice thickness. Results: The thickness of the slice‐selective inversion in 2D interleaved multislice AMIRA should be doubled compared with the manufacturer's standard setting to avoid an increased sensitivity to flow and pulsation effects particularly in the CSF. However, this solution also limits its practical applicability, as slices located at directly adjacent vertebrae cannot be imaged together. Successful interleaved two‐slice AMIRA imaging for a "reference" in vivo protocol with 0.50 × 0.50 mm2 in‐plane resolution and 8‐mm slice thickness is demonstrated, therefore halving its acquisition time per slice from 3 min down to 1.5 min. Conclusion: The investigated 2D interleaved two‐slice AMIRA variant facilitates spinal cord imaging that maintains similar contrast and the same resolution as the conventional 2D single‐slice AMIRA approach, but does so with a halved acquisition time. [ABSTRACT FROM AUTHOR]

Background and purpose: In amyotrophic lateral sclerosis (ALS), there is an unmet need for more precise patient characterization through quantitative, ideally operator‐independent, assessments of disease extent and severity. Radially sampled averaged magnetization inversion recovery acquisitions (rAMIRA) magnetic resonance imaging enables gray matter (GM) and white matter (WM) area quantitation in the cervical and thoracic spinal cord (SC) with optimized contrast. We aimed to investigate rAMIRA‐derived SC GM and SC WM areas and their association with clinical phenotype and disability in ALS. Methods: A total of 36 patients with ALS (mean [SD] age 61.7 [12.6] years, 14 women) and 36 healthy, age‐ and sex‐matched controls (HCs; mean [SD] age 63.1 [12.1] years, 14 women) underwent two‐dimensional axial rAMIRA imaging at the inter‐vertebral disc levels C2/3–C5/C6 and the lumbar enlargement level Tmax. ALS Functional Rating Scale–revised (ALSFRS‐R) score, muscle strength, and sniff nasal inspiratory pressure (SNIP) were assessed. Results: Compared to HCs, GM and WM areas were reduced in patients at all cervical levels (p < 0.0001). GM area (p = 0.0001), but not WM area, was reduced at Tmax. Patients with King's Stage 3 showed significant GM atrophy at all levels, while patients with King's Stage 1 showed significant GM atrophy selectively at Tmax. SC GM area was significantly associated with muscle force at corresponding myotomes. GM area at C3/C4 was associated with ALSFRS‐R (p < 0.001) and SNIP (p = 0.0016). Conclusion: Patients with ALS assessed by rAMIRA imaging show significant cervical and thoracic SC GM and SC WM atrophy. SC GM area correlates with muscle strength and clinical disability. GM area reduction at Tmax may be an early disease sign. Longitudinal studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Spinal cord (SC) gray and white matter pathology plays a central role in multiple sclerosis (MS). Objective: We aimed to investigate the extent, pattern, and clinical relevance of SC gray and white matter atrophy in vivo. Methods: 39 relapsing–remitting patients (RRMS), 40 progressive MS patients (PMS), and 24 healthy controls (HC) were imaged at 3T using the averaged magnetization inversion recovery acquisitions sequence. Total and lesional cervical gray and white matter, and posterior (SCPH) and anterior horn (SCAH) areas were automatically quantified. Clinical assessment included the expanded disability status scale, timed 25-foot walk test, nine-hole peg test, and the 12-item MS walking scale. Results: PMS patients had significantly reduced cervical SCAH — but not SCPH — areas compared with HC and RRMS (both p < 0.001). In RRMS and PMS, the cervical SCAH areas increased significantly less in the region of cervical SC enlargement compared with HC (all p < 0.001). This reduction was more pronounced in PMS compared with RRMS (both p < 0.001). In PMS, a lower cervical SCAH area was the most important magnetic resonance imaging (MRI)-variable for higher disability scores. Conclusion: MS patients show clinically relevant cervical SCAH atrophy, which is more pronounced in PMS and at the level of cervical SC enlargement. [ABSTRACT FROM AUTHOR]

Objective: To determine if patients with post‐polio syndrome (PPS) show spinal cord gray matter (SCGM) atrophy and to assess associations between SCGM atrophy, muscle strength and patient‐reported functional decline. Methods: Twenty patients diagnosed with PPS (March of Dimes criteria) and 20 age‐ and sex‐matched healthy controls (HC) underwent 3T axial 2D‐rAMIRA magnetic resonance imaging at the intervertebral disc levels C2/C3–C6/C7, T9/T10 and the lumbar enlargement level (Tmax) (0.5 × 0.5 mm2 in‐plane resolution). SCGM areas were segmented manually by two independent raters. Muscle strength, self‐reported fatigue, depression and pain measures were assessed. Results: Post‐polio syndrome patients showed significantly and preferentially reduced SCGM areas at C2/C3 (p = 0.048), C3/C4 (p = 0.001), C4/C5 (p < 0.001), C5/C6 (p = 0.004) and Tmax (p = 0.041) compared to HC. SCGM areas were significantly associated with muscle strength in corresponding myotomes even after adjustment for fatigue, pain and depression. SCGM areaTmax together with age and sex explained 68% of ankle dorsiflexion strength variance. No associations were found with age at or time since infection. Patients reporting PPS‐related decline in arm function showed significant cervical SCGM atrophy compared to stable patients adjusted for initial disease severity. Conclusions: Patients with PPS show significant SCGM atrophy that correlates with muscle strength and is associated with PPS‐related functional decline. Our findings suggest a secondary neurodegenerative process underlying SCGM atrophy in PPS that is not explained by aging or residua of the initial infection alone. Confirmation by longitudinal studies is needed. The described imaging methodology is promising for developing novel imaging surrogates for SCGM diseases. [ABSTRACT FROM AUTHOR]

Abstract Background Contrast enhanced cardiovascular magnetic resonance (CMR) with T1 mapping enables quantification of diffuse myocardial fibrosis. Various factors, however, can interfere with T1 measurements. The purpose of the current study was to assess the effect of co-medication with a typical protein binding drug (Ibuprofen) on T1 values in vitro and in vivo. Methods 50 vials were prepared with different concentrations of gadobenate dimeglumine, Ibuprofen and human serum albumin in physiologic NaCl solution and imaged at 1.5T with a spin echo sequence at multiple TRs to measure T1 values and calculate relaxivities. 10 volunteers (5 men; 31±6.3 years) were imaged at 1.5T. T1 values for myocardium and blood pool were determined for various time points after administration of 0.15mmol/kg gadobenate dimeglumine using a modified look-locker inversion-recovery sequence before and after administration of Ibuprofen over 24 hours. The partition coefficient was calculated as ΔR1myocardium/ΔR1blood, where R1=1/T1. Results In vitro no significant correlation was found between relaxivity and Ibuprofen concentration, neither in absence (r=−0.15, p=0.40) nor in presence of albumin (r=−0.32, p=0.30). In vivo there was no significant difference in post contrast T1 times of myocardium and blood, respectively and also in the partition coefficient between exam 1 and 2 (p>0.05). There was good agreement of the T1 times of myocardium and blood and the partition coefficient, respectively between exam 1 and 2. Conclusions Contrast enhanced T1 mapping is unaffected by co-medication with the protein binding substance Ibuprofen and has an excellent reproducibility.

Background: MR imaging of the spinal cord (SC) gray matter (GM) at the cervical and lumbar enlargements' level may be particularly informative in lower motor neuron disorders, e. g., spinal muscular atrophy, but also in other neurodegenerative or autoimmune diseases affecting the SC. Radially sampled averaged magnetization inversion recovery acquisition (rAMIRA) is a novel approach to perform SC imaging in clinical settings with favorable contrast and is well-suited for SC GM quantitation. However, before applying rAMIRA in clinical studies, it is important to understand (i) the sources of inter-subject variability of total SC cross-sectional areas (TCA) and GM area (GMA) measurements in healthy subjects and (ii) their relation to age and sex to facilitate the detection of pathology-associated changes. In this study, we aimed to develop normalization strategies for rAMIRA-derived SC metrics using skull and spine-based metrics to reduce anatomical variability. Methods: Sixty-one healthy subjects (age range 11–93 years, 37.7% women) were investigated with axial two-dimensional rAMIRA imaging at 3T MRI. Cervical and thoracic levels including the level of the cervical (C4/C5) and lumbar enlargements (Tmax) were examined. SC T2-weighted sagittal images and high-resolution 3D whole-brain T1-weighted images were acquired. TCA and GMAs were quantified. Anatomical variables with associations of | r | > 0.30 in univariate association with SC areas, and age and sex were used to construct normalization models using backward selection with TCAC4/C5 as outcome. The effect of the normalization was assessed by % relative standard deviation (RSD) reductions. Results: Mean inter-individual variability and the SD of the SC area metrics were considerable: TCAC4/5: 8.1%/9.0; TCATmax: 8.9%/6.5; GMAC4/C5: 8.6%/2.2; GMATmax: 12.2%/3.8. Normalization based on sex, brain WM volume, and spinal canal area resulted in RSD reductions of 23.7% for TCAs and 12.0% for GM areas at C4/C5. Normalizations based on the area of spinal canal alone resulted in RSD reductions of 10.2% for TCAs and 9.6% for GM areas at C4/C5, respectively. Discussion: Anatomic inter-individual variability of SC areas is substantial. This study identified effective normalization models for inter-subject variability reduction in TCA and SC GMA in healthy subjects based on rAMIRA imaging. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine if parameters derived from diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) can help to assess early response to peptide receptor radionuclide therapy (PRRT) with 90Y-DOTATOC in neuroendocrine hepatic metastases (NET-HM). Twenty patients (10 male; 10 female; mean age: 59.2 years) with NET-HM were prospectively enrolled in this single-center imaging study. DW-MRI and DCE-MRI studies were performed just before and 48 hours after therapy with 90Y-DOTATOC. Abdominal SPECT/CT was performed 24 hours after therapy. This MRI imaging and therapy session was repeated after a mean interval of 10 weeks. Up to four lesions per patient were evaluated. Response to therapy was evaluated using metastasis sizes at the first and second therapy session as standard for comparison (regressive, stable, and progressive). DW-MRI analysis included the apparent diffusion coefficient (ADC) and parameters related to intravoxel incoherent motion (IVIM), namely, diffusion (D), perfusion fraction (f) and pseudo-diffusion ( D ∗ ). DCE-MRI analysis comprised Ktrans, v e and kep. For statistical analysis of group differences, one-way analysis of variance (ANOVA) and appropriate post hoc testing was performed. A total of 51 lesions were evaluated. Seven of 51 lesions (14%) showed size progression, 18/51 (35%) regression, and 26/51 (51%) remained stable. The lesion-to-spleen uptake ratio in SPECT showed a decrease between the two treatment sessions that was significantly stronger in regressive lesions compared with stable (p = 0.013) and progressive lesions (p = 0.021). ANOVA showed significant differences in mean ADC after 48 h (p = 0.026), with higher ADC values for regressive lesions. Regarding IVIM, highest values for D at baseline were seen in regressive lesions (p = 0.023). In DCE-MRI, a statistically significant increase in v e after 10 weeks (p = 0.046) was found in regressive lesions. No differences were observed for the transfer constants Ktrans and kep. Diffusion restriction quantified as ADC was able to differentiate regressive from progressive NET-HMs as early as 48 hours after PRRT. DW-MRI therefore may complement scintigraphy/SPECT for early assessment of response to PRRT. Assessment of perfusion parameters using IVIM and DCE-MRI did not show an additional benefit. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction: Quantitative MRI techniques detect disease progression in myopathies more sensitively than muscle function measures or conventional MRI. To date, only conventional MRI data using visual rating scales are available for measurement of disease progression in Becker muscular dystrophy (BMD). Methods: In 3 patients with BMD (mean age 36.8 years), the mean fat fraction (MFF) of the thigh muscles was assessed by MRI at baseline and at 1-year follow-up using a 2-point Dixon approach (2PD). The motor function measurement scale (MFM) was used for clinical assessment. Results: The mean MFF of all muscles at baseline was 61.6% (SD 7.6). It increased by 3.7% to 65.3% (SD 4.7) at follow-up. The severity of muscle involvement varied between various muscle groups. Conclusions: As in other myopathies, 2PD can quantify fatty muscle degeneration in BMD and can detect disease progression in a small sample size and at relatively short imaging intervals. Muscle Nerve 51: 918-921, 2015 [ABSTRACT FROM AUTHOR]

• Utilization of a motion-insensitive radial acquisition for spinal cord MRI. • First morphometric MRI approach with a particular focus on the thoracic spinal cord. • Contrast adaptation based on averaged magnetization inversion recovery acquisitions. • Strong contrast between gray and white matter allows quantitative volumetry. • Proof-of-concept for spinal muscular atrophy and post-polio syndrome. Spinal cord (SC) gray and white matter atrophy quantification by advanced morphometric MRI can help to better characterize the course of neurodegenerative diseases in vivo, such as e.g. lower motor neuron disorders. Imaging the lower thoracic cord - containing those motor neurons that control leg function - could be particularly informative, however, is challenging due to tissue composition, physiological motion and large field of views. An "averaged magnetization inversion recovery acquisitions" (AMIRA) approach with a radial k-space acquisition scheme was developed. The method is designed for morphometric SC imaging with a focus on the thoracic SC. In a typical setting, radial AMIRA acquires transverse slices with a high 0.50 × 0.50mm2 in-plane resolution and a pronounced positive contrast between thoracic gray and white matter, within typically 2:39 min. Additional proof-of-concept measurements in patients demonstrate that such contrast and resolving capability is indeed necessary to assess potential atrophy of the anterior horns. Radial AMIRA utilizes two benefits of radial MRI techniques: being generally less prone to motion effects and that fold over artifacts can manifest less intrusively. These benefits are united with the original AMIRA approach which allows the contrast to be 'tuned' and improved based on the combination of five simultaneously acquired images of different tissue contrast. Radial AMIRA is a promising approach for in vivo SC gray and white matter atrophy visualization and quantification in lower motor neuron diseases and other autoimmune or genetic diseases involving the entire (not only cervical) spinal cord. [ABSTRACT FROM AUTHOR]

Background Radially sampled averaged magnetization inversion-recovery acquisition (rAMIRA) imaging shows hyperintensity in the lateral corticospinal tract (CST) in patients with motor neuron diseases. Purpose To systematically determine the accuracy of the lateral corticospinal tract sign for detecting patients with amyotrophic lateral sclerosis (ALS) at rAMIRA MRI. Materials and Methods This study included prospectively acquired data from participants in ALS and other motor neuron disease imaging studies at the University Hospital Basel, Switzerland. All participants underwent 3-T axial two-dimensional rAMIRA imaging at four cervical intervertebral disk levels. The lateral CST sign was defined as spinal cord white matter hyperintensity dorsolateral to the anterior horns, with higher signal intensity than in the dorsal columns on axial rAMIRA images. Marker accuracy was assessed in a study data set and in an independent validation data set. Postmortem rAMIRA imaging and histopathologic analysis were performed in one participant who died during the study. Results Participants with ALS (study data set: 38 participants [mean age, 61 years; IQR, 15 years], 22 male participants; validation data set: 10 participants [mean age, 61 years; IQR, 21 years], seven male participants), post-polio syndrome (study data set: 25 participants [mean age, 68 years; IQR, 8 years], 12 male participants), spinal muscular atrophy (study data set: 10 participants [mean age, 43 years; IQR, 14 years], eight male participants; validation data set: five participants [mean age, 38 years; IQR, 19 years], two male participants), and healthy control participants (study data set: 60 participants [mean age, 57 years; IQR, 20 years], 36 male participants; validation data set: 10 participants [mean age, 44 years; IQR, 17 years], seven male participants) were included. The sensitivity and specificity of rAMIRA for ALS were 60% (23 of 38) and 97% (91 of 94) in the study data set and 100% (10 of 10) and 93% (14 of 15) in the validation data set, respectively. Histopathologic analysis showed distinct loss of myelinated axons in the localization of the hyperintensities observed at rAMIRA imaging performed in situ and after organ extraction. Conclusion The recently defined marker at rAMIRA MRI may be a promising tool for assessing upper motor neuron degeneration in the lateral CST in patients with ALS. Clinical trials registration no. NCT03561623, NCT05764434, NCT06137612 © RSNA, 2024 Supplemental material is available for this article.

Background: Spinal cord (SC) gray and white matter pathology plays a central role in multiple sclerosis (MS)., Objective: We aimed to investigate the extent, pattern, and clinical relevance of SC gray and white matter atrophy in vivo., Methods: 39 relapsing-remitting patients (RRMS), 40 progressive MS patients (PMS), and 24 healthy controls (HC) were imaged at 3T using the averaged magnetization inversion recovery acquisitions sequence. Total and lesional cervical gray and white matter, and posterior (SCPH) and anterior horn (SCAH) areas were automatically quantified. Clinical assessment included the expanded disability status scale, timed 25-foot walk test, nine-hole peg test, and the 12-item MS walking scale., Results: PMS patients had significantly reduced cervical SCAH - but not SCPH - areas compared with HC and RRMS (both p  < 0.001). In RRMS and PMS, the cervical SCAH areas increased significantly less in the region of cervical SC enlargement compared with HC (all p  < 0.001). This reduction was more pronounced in PMS compared with RRMS (both p  < 0.001). In PMS, a lower cervical SCAH area was the most important magnetic resonance imaging (MRI)-variable for higher disability scores., Conclusion: MS patients show clinically relevant cervical SCAH atrophy, which is more pronounced in PMS and at the level of cervical SC enlargement.

The purpose of this study was to determine if parameters derived from diffusion-weighted (DW-) and dynamic contrast-enhanced (DCE-) magnetic resonance imaging (MRI) can help to assess early response to peptide receptor radionuclide therapy (PRRT) with 90 Y-DOTATOC in neuroendocrine hepatic metastases (NET-HM). Twenty patients (10 male; 10 female; mean age: 59.2 years) with NET-HM were prospectively enrolled in this single-center imaging study. DW-MRI and DCE-MRI studies were performed just before and 48 hours after therapy with 90 Y-DOTATOC. Abdominal SPECT/CT was performed 24 hours after therapy. This MRI imaging and therapy session was repeated after a mean interval of 10 weeks. Up to four lesions per patient were evaluated. Response to therapy was evaluated using metastasis sizes at the first and second therapy session as standard for comparison (regressive, stable, and progressive). DW-MRI analysis included the apparent diffusion coefficient (ADC) and parameters related to intravoxel incoherent motion (IVIM), namely, diffusion ( D ), perfusion fraction ( f ) and pseudo-diffusion ( D ∗ ). DCE-MRI analysis comprised K trans , v e and k ep . For statistical analysis of group differences, one-way analysis of variance (ANOVA) and appropriate post hoc testing was performed. A total of 51 lesions were evaluated. Seven of 51 lesions (14%) showed size progression, 18/51 (35%) regression, and 26/51 (51%) remained stable. The lesion-to-spleen uptake ratio in SPECT showed a decrease between the two treatment sessions that was significantly stronger in regressive lesions compared with stable ( p = 0.013) and progressive lesions ( p = 0.021). ANOVA showed significant differences in mean ADC after 48 h ( p = 0.026), with higher ADC values for regressive lesions. Regarding IVIM, highest values for D at baseline were seen in regressive lesions ( p = 0.023). In DCE-MRI, a statistically significant increase in v e after 10 weeks ( p = 0.046) was found in regressive lesions. No differences were observed for the transfer constants K trans and k ep . Diffusion restriction quantified as ADC was able to differentiate regressive from progressive NET-HMs as early as 48 hours after PRRT. DW-MRI therefore may complement scintigraphy/SPECT for early assessment of response to PRRT. Assessment of perfusion parameters using IVIM and DCE-MRI did not show an additional benefit., Competing Interests: Markus Klarhöfer is an employee of Siemens Healthcare AG (Switzerland) and declares no conflicts of interest regarding this study. All other authors declare that they have no conflicts of interest., (Copyright © 2019 Thomas Weikert et al.)

The development of new therapeutic agents for the treatment of Duchenne muscular dystrophy has put a focus on defining outcome measures most sensitive to capture treatment effects. This cross-sectional analysis investigates the relation between validated clinical assessments such as the 6-minute walk test, motor function measure and quantitative muscle MRI of thigh muscles in ambulant Duchenne muscular dystrophy patients, aged 6.5 to 10.8 years (mean 8.2, SD 1.1). Quantitative muscle MRI included the mean fat fraction using a 2-point Dixon technique, and transverse relaxation time (T2) measurements. All clinical assessments were highly significantly inter-correlated with p < 0.001. The strongest correlation with the motor function measure and its D1-subscore was shown by the 6-minute walk test. Clinical assessments showed no correlation with age. Importantly, quantitative muscle MRI values significantly correlated with all clinical assessments with the extensors showing the strongest correlation. In contrast to the clinical assessments, quantitative muscle MRI values were highly significantly correlated with age. In conclusion, the motor function measure and timed function tests measure disease severity in a highly comparable fashion and all tests correlated with quantitative muscle MRI values quantifying fatty muscle degeneration., (Copyright © 2017 Elsevier B.V. All rights reserved.)