Skeletal muscle quantitative nuclear magnetic resonance imaging follow-up of adult Pompe patients.
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ABSTRACT:
SUBMITTER: Carlier PG
PROVIDER: S-EPMC4432102 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundLate-onset Pompe disease (LOPD) is a genetic disorder characterized by progressive degeneration of the skeletal muscles produced by a deficiency of the enzyme acid alpha-glucosidase. Enzymatic replacement therapy with recombinant human alpha-glucosidase seems to reduce the progression of the disease; although at the moment, it is not completely clear to what extent. Quantitative muscle magnetic resonance imaging (qMRI) is a good biomarker for the follow-up of fat replacement in neuromuscular disorders. The aim of this study was to describe the changes observed in fat replacement in skeletal muscles using qMRI in a cohort of LOPD patients followed prospectively.MethodsA total of 36 LOPD patients were seen once every year for 4 years. qMRI, several muscle function tests, spirometry, activities of daily living scales, and quality-of-life scales were performed on each visit. Muscle MRI consisted of two-point Dixon studies of the trunk and thigh muscles. Computer analysis of the images provided the percentage of muscle degenerated and replaced by fat in every muscle (known as fat fraction). Longitudinal analysis of the measures was performed using linear mixed models applying the Greenhouse-Geisser test.ResultsWe detected a statistically significant and continuous increase in mean thigh fat fraction both in treated (+5.8% in 3 years) and in pre-symptomatic patients (+2.6% in 3years) (Greenhouse-Geisser p < 0.05). As an average, fat fraction increased by 1.9% per year in treated patients, compared with 0.8% in pre-symptomatic patients. Fat fraction significantly increased in every muscle of the thighs. We observed a significant correlation between changes observed in fat fraction in qMRI and changes observed in the results of the muscle function tests performed. Moreover, we identified that muscle performance and mean thigh fat fraction at baseline visit were independent parameters influencing fat fraction progression over 4 years (analysis of covariance, p < 0.05).ConclusionsOur study identifies that skeletal muscle fat fraction continues to increase in patients with LOPD despite the treatment with enzymatic replacement therapy. These results suggest that the process of muscle degeneration is not stopped by the treatment and could impact muscle function over the years. Hereby, we show that fat fraction along with muscle function tests can be considered a good outcome measures for clinical trials in LOPD patients.
| S-EPMC7432562 | biostudies-literature
Project description:Late onset Pompe disease (LOPD) is a slow, progressive disorder characterized by skeletal and respiratory muscle weakness. Enzyme replacement therapy (ERT) slows down the progression of muscle symptoms. Reliable biomarkers are needed to follow up ERT-treated and asymptomatic LOPD patients in clinical practice. In this study, 32 LOPD patients (22 symptomatic and 10 asymptomatic) underwent muscle MRI using 3-point Dixon and were evaluated at the time of the MRI with several motor function tests and patient-reported outcome measures, and again after one year. Muscle MRI showed a significant increase of 1.7% in the fat content of the thigh muscles in symptomatic LOPD patients. In contrast, there were no noteworthy differences between muscle function tests in the same period of time. We did not observe any significant changes either in muscle MRI or in muscle function tests in asymptomatic patients over the year. We conclude that 3-point Dixon muscle MRI is a useful tool for detecting changes in muscle structure in symptomatic LOPD patients and could become part of the current follow-up protocol in daily clinics.
| S-EPMC6052002 | biostudies-literature
Project description: Not available
| S-EPMC3461694 | biostudies-literature
Project description:ObjectiveSince the introduction of enzyme replacement therapy (ERT) with alglucosidase alfa, there has been increased survival in patients with Pompe disease. It is essential to characterize and quantify the burden of disease in these patients. Here, we report a measure of muscle fat infiltration in children with infantile and pediatric late-onset Pompe disease (IPD and LOPD, respectively) to better understand the extent of muscle involvement.MethodsEleven pediatric patients with Pompe disease (five IPD, six LOPD), ages 7-17 years, received whole-body magnetic resonance imaging (WBMRI), muscle strength testing using the modified Medical Research Council (mMRC) scale, functional assessment using gait, stairs, gowers, chair (GSGC), and urine glucose tetrasaccharide (Glc4) testing. The intramuscular fat seen on WBMRI was quantified using proton density fat fraction (PDFF) and correlated to appropriate muscle strength and functional tests, and urine Glc4.ResultsPatients with IPD, although younger, had higher mean PDFF values than LOPD patients (11.61% vs 8.52%). Significant correlation existed between PDFF and the GSGC assessment (r = .9273, P = .0003). Moderate correlation existed between PDFF and mMRC (r = -.667, P = .0831), and PDFF and urine Glc4 (r = .6121, P = .0667). Anterior tibialis was in the top quartile of muscle involvement for patients with LOPD.ConclusionIn the past, physical therapy assessments alone have been used to track disease progression. Here, we show the clinical utility of WBMRI in quantifying muscle involvement in children with Pompe disease, especially regarding the novel involvement of anterior tibialis in children with LOPD, to better assess baseline muscle burden and mapping disease progression in children treated with ERT.
| S-EPMC7802624 | biostudies-literature
Project description:ObjectiveTo characterize muscle involvement and evaluate disease severity in patients with GNE myopathy using skeletal muscle MRI and proton magnetic resonance spectroscopy (1H-MRS).MethodsSkeletal muscle imaging of the lower extremities was performed in 31 patients with genetically confirmed GNE myopathy, including T1-weighted and short tau inversion recovery (STIR) images, T1 and T2 mapping, and 1H-MRS. Measures evaluated included longitudinal relaxation time (T1), transverse relaxation time (T2), and 1H-MRS fat fraction (FF). Thigh muscle volume was correlated with relevant measures of strength, function, and patient-reported outcomes.ResultsThe cohort was representative of a wide range of disease progression. Contractile thigh muscle volume ranged from 5.51% to 62.95% and correlated with thigh strength (r = 0.91), the 6-minute walk test (r = 0.82), the adult myopathy assessment tool (r = 0.83), the activities-specific balance confidence scale (r = 0.65), and the inclusion body myositis functional rating scale (r = 0.62). Four stages of muscle involvement were distinguished by qualitative (T1W and STIR images) and quantitative methods: stage I: unaffected muscle (T1 = 1,033 ± 74.2 ms, T2 = 40.0 ± 1.9 ms, FF = 7.4 ± 3.5%); stage II: STIR hyperintense muscle with minimal or no fat infiltration (T1 = 1,305 ± 147 ms, T2 = 50.2 ± 3.5 ms, FF = 27.6 ± 12.7%); stage III: fat infiltration and STIR hyperintensity (T1 = 1,209 ± 348 ms, T2 = 73.3 ± 12.6 ms, FF = 57.5 ± 10.6%); and stage IV: complete fat replacement (T1 = 318 ± 39.9 ms, T2 = 114 ± 21.2 ms, FF = 85.6 ± 4.2%). 1H-MRS showed a significant decrease in intramyocellular lipid and trimethylamines between stage I and II, suggesting altered muscle metabolism at early stages.ConclusionMRI biomarkers can monitor muscle involvement and determine disease severity noninvasively in patients with GNE myopathy.Clinicaltrialsgov identifierNCT01417533.
| S-EPMC7884988 | biostudies-literature
Project description:The current state-of-the-art diagnosis method for deep tissue injury in muscle, a subcategory of pressure ulcers, is palpation. It is recognized that deep tissue injury is frequently preceded by altered biomechanical properties. A quantitative understanding of the changes in biomechanical properties preceding and during deep tissue injury development is therefore highly desired. In this paper we quantified the spatial-temporal changes in mechanical properties upon damage development and recovery in a rat model of deep tissue injury. Deep tissue injury was induced in nine rats by two hours of sustained deformation of the tibialis anterior muscle. Magnetic resonance elastography (MRE), T2 -weighted, and T2 -mapping measurements were performed before, directly after indentation, and at several timepoints during a 14-day follow-up. The results revealed a local hotspot of elevated shear modulus (from 3.30 ± 0.14 kPa before to 4.22 ± 0.90 kPa after) near the center of deformation at Day 0, whereas the T2 was elevated in a larger area. During recovery there was a clear difference in the time course of the shear modulus and T2 . Whereas T2 showed a gradual normalization towards baseline, the shear modulus dropped below baseline from Day 3 up to Day 10 (from 3.29 ± 0.07 kPa before to 2.68 ± 0.23 kPa at Day 10, P < 0.001), followed by a normalization at Day 14. In conclusion, we found an initial increase in shear modulus directly after two hours of damage-inducing deformation, which was followed by decreased shear modulus from Day 3 up to Day 10, and subsequent normalization. The lower shear modulus originates from the moderate to severe degeneration of the muscle. MRE stiffness values were affected in a smaller area as compared with T2 . Since T2 elevation is related to edema, distributing along the muscle fibers proximally and distally from the injury, we suggest that MRE is more specific than T2 for localization of the actual damaged area.
| S-EPMC6593838 | biostudies-literature
Project description:BackgroundLöffler endocarditis is a condition characterized by cardiac infiltration of eosinophils. Cardiac magnetic resonance imaging (MRI) is a modality for the diagnosis of myocardial damage.Case summaryThis is the case of a 77-year-old man with acute decompensated heart failure who was admitted. Transthoracic echocardiography showed preserved left ventricular (LV) systolic function along with LV thrombi attached to the septo-apical wall and the posterior wall, consistent with Löffler endocarditis. Cardiac MRI revealed obliteration of the LV apex and partial filling of the LV cavity, as well as near circumferential subendocardial late gadolinium enhancement (LGE) in the mid- and apical segments. T2-weighted images showed a near circumferential high-intensity area of the LV subendocardial muscle in the mid- and apical segments. High-dose corticosteroids and intravenous heparin were initiated, followed by maintenance warfarin therapy. At 18 months, follow-up cardiac MRI revealed the disappearance of the LV thrombi, and a reduction of LGE, as well as high-intensity areas in the T2-weighted images.DiscussionThe high-intensity area of T2-weighted images indicate the presence of subendocardial oedema. Eosinophil-mediated heart damage evolves through three stages: (i) acute necrotic, (ii) thrombotic, and (iii) fibrotic stages. Since the deposition of toxic eosinophil granule proteins and eosinophil infiltration injured the endocardium, the first-line treatment for Löffler endocarditis is corticosteroid therapy. In this case, LGE in the subendocardium and the high-intensity area in the T2-weighted images were reduced at 18 months. High-intensity areas of T2-weighted images in the acute phase might indicate the possibility of therapeutic response to corticosteroid therapy.
| S-EPMC7793205 | biostudies-literature
Project description:Myocarditis is a rare complication of the COVID-19 mRNA vaccine. We previously reported a case series of 15 adolescents with vaccine-associated myocarditis, 87% of whom had abnormalities on initial cardiac magnetic resonance (CMR), including late gadolinium enhancement (LGE) in 80%. We performed follow-up CMRs to determine the trajectory of myocardial recovery and better understand the natural history of vaccine-associated myocarditis. Case series of patients age < 19 years admitted to Boston Children's Hospital with acute vaccine-associated myocarditis following the BNT162b2 vaccine who had abnormal CMR at the time of initial presentation, and underwent follow-up testing. CMR assessment included left ventricular (LV) ejection fraction, T2-weighted myocardial imaging, LV global native T1, LV global T2, extracellular volume (ECV), and late gadolinium enhancement (LGE). Ten patients (9 male, median age 15 years) with vaccine-associated myocarditis underwent follow-up CMR at a median of 92 days (range 76-119) after hospital discharge. LGE was persistent in 80% of patients, though improved from prior in all cases. Two patients (20%) had abnormal LV global T1 at presentation, which normalized on follow-up. ECV decreased between acute presentation and follow-up in 6/10 patients; it remained elevated at follow-up in 1 patient and borderline in 3 patients.ConclusionCMR performed ~3 months after admission for COVID-19 vaccine-associated myocarditis showed improvement of LGE in all patients, but persistent in the majority. Follow-up CMR 6-12 months after acute episode should be considered to better understand the long-term cardiac risks.What is known• Myocarditis is a rare side effect of COVID-19 mRNA vaccine. •Late gadolinium enhancement is present on most cardiac magnetic resonance at the time of acute presentation.What is new•Late gadolinium enhancement improved on all repeat cardiac magnetic resonance at 3-month follow-up. •Most patients still had a small amount of late gadolinium enhancement, the clinical significance of which is yet to be determined.
| S-EPMC9046711 | biostudies-literature
Project description:Fibrosis is a key pathological feature in muscle disorders, but its quantification mainly relies on histological and biochemical assays. Muscle fibrosis most frequently is entangled with other pathological processes, as cell membrane lesions, inflammation, necrosis, regeneration, or fatty infiltration, making in vivo assessment difficult. Here, we (1) describe a novel mouse model with variable levels of induced skeletal muscle fibrosis displaying minimal inflammation and no fat infiltration, and (2) report how fibrosis affects non-invasive metrics derived from nuclear magnetic resonance (NMR) and ultrasound shear-wave elastography (SWE) associated with a passive biomechanical assay. Our findings show that collagen fraction correlates with multiple non-invasive metrics. Among them, muscle stiffness as measured by SWE, T2, and extracellular volume (ECV) as measured by NMR have the strongest correlations with histology. We also report that combining metrics in a multi-modality index allowed better discrimination between fibrotic and normal skeletal muscles. This study demonstrates that skeletal muscle fibrosis leads to alterations that can be assessed in vivo with multiple imaging parameters. Furthermore, combining NMR and SWE passive biomechanical assay improves the non-invasive evaluation of skeletal muscle fibrosis and may allow disentangling it from co-occurring pathological alterations in more complex scenarios, such as muscular dystrophies.
| S-EPMC7801669 | biostudies-literature
Project description:BackgroundCardiac magnetic resonance (CMR) can detect inflammatory myocardial alterations in patients suspected of having acute myocarditis. There is limited information regarding the degree of normalization of CMR parameters during the course of the disease and the time window during which quantitative CMR should be most reasonably implemented for diagnostic work-up.Methods and resultsTwenty-four patients with suspected acute myocarditis and 45 control subjects underwent CMR. Initial CMR was performed 2.6±1.9 days after admission. Myocarditis patients underwent CMR follow-up after 2.4±0.6, 5.5±1.3, and 16.2±9.9 weeks. The CMR protocol included assessment of standard Lake Louise criteria, T1 relaxation times, extracellular volume fraction, and T2 relaxation times. Group differences between myocarditis patients and control subjects were highest in the acute stage of the disease (P<0.001 for all parameters). There was a significant and consistent decrease in all inflammatory CMR parameters over the course of the disease (P<0.01 for all parameters). Myocardial T1 and T2 relaxation times-indicative of myocardial edema-were the only single parameters showing significant differences between myocarditis patients and control subjects on 5.5±1.3-week follow-up (T1: 986.5±44.4 ms versus 965.1±28.1 ms, P=0.022; T2: 55.5±3.2 ms versus 52.6±2.6 ms; P=0.001).ConclusionsIn patients with acute myocarditis, CMR markers of myocardial inflammation demonstrated a rapid and continuous decrease over several follow-up examinations. CMR diagnosis of myocarditis should therefore be attempted at an early stage of the disease. Myocardial T1 and T2 relaxation times were the only parameters of active inflammation/edema that could discriminate between myocarditis patients and control subjects even at a convalescent stage of the disease.
| S-EPMC5015395 | biostudies-literature