Different Approaches to Analyze Muscle Fat Replacement With Dixon MRI in Pompe Disease

Quantitative MRI is an increasingly used method to monitor disease progression in muscular disorders due to its ability to measure changes in muscle fat content (reported as fat fraction) over a short period. Being able to objectively measure such changes is crucial for the development of new treatments in clinical trials. However, the analysis of the images involved continues to be a daunting task because of the time needed. Whether a more specific analysis selecting individual muscles or a global one analyzing the whole thigh or compartments could be a suitable alternative has only been marginally studied. In our study we compare three methods of analysis of 2-point-dixon images in a cohort of 34 patients with late onset Pompe disease followed over a period of one year. We measured fat fraction on MRIs obtained at baseline and at year 1, and we calculated the increment of fat fraction. We correlated the results obtained with the results of muscle function tests to investigate whether the three methods of analysis were equivalent or not. We observed significant differences between the three methods in the estimation of the fat fraction at both baseline and year 1, but no difference was found in the increment in fat fraction between baseline and year 1. When we correlated the fat fraction obtained with each method and the muscle function tests, we found a significant correlation with most tests in all three methods, although in most comparisons the highest correlation coefficient was found with the analysis of individual muscles. We conclude that the fastest strategy of analysis assessing compartments or the whole thigh could be reliable for certain cohorts of patients where the variable to study is the fat increment. In other sorts of studies, an individual muscle approach seems the most reliable technique.

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Correlation Between Respiratory Accessory Muscles and Diaphragm Pillars MRI and Pulmonary Function Test in Late-Onset Pompe Disease Patients

Frontiers in Neurology ◽

10.3389/fneur.2021.621257 ◽

2021 ◽

Vol 12 ◽

Author(s):

David Reyes-Leiva ◽

Jorge Alonso-Pérez ◽

Mercedes Mayos ◽

Claudia Nuñez-Peralta ◽

Jaume Llauger ◽

...

Keyword(s):

Pompe Disease ◽

Muscle Function ◽

Respiratory Muscle ◽

Late Onset ◽

Respiratory Support ◽

Fat Replacement ◽

Function Tests ◽

Fat Fraction ◽

Muscle Groups ◽

Over Time

Objectives: Pompe disease is a rare genetic disease produced by mutations in the GAA gene leading to progressive skeletal and respiratory muscle weakness. T1-weighted magnetic resonance imaging is useful to identify fatty replacement in skeletal muscles of late-onset Pompe disease (LOPD) patients. Previous studies have shown that replacement by fat correlates with worse results of muscle function tests. Our aim was to investigate if fat replacement of muscles involved in the ventilation process correlated with results of the spirometry and predicted respiratory muscle impairment in LOPD patients over time.Materials and Methods: We studied a cohort of 36 LOPD patients followed up annually in our center for a period of 4 years. We quantified muscle fat replacement using Mercuri score of the thoracic paraspinal and abdominal muscles and the pillars of the diaphragm. We correlated the combined Mercuri scores of these areas with spirometry results and the need of respiratory support.Results: We found a statistically significant correlation (Spearman test, p < 0.05; coefficient of correlation > 0.6) between forced vital capacity seated and lying and fat fraction score of all muscle groups studied. The group of patients who needed respiratory support had higher fat fraction scores than patients not requiring ventilatory support. Higher fat replacement in these areas correlated with worse progression in spirometry values over time.Conclusions: Fat replacement of paraspinal, abdominal, and trunk muscles correlates with results of spirometry and is able to predict worsening in respiratory muscle function tests that could lead to an emerging ventilatory dysfunction. Therefore, the identification of fat replacement in these muscle groups should lead to a closer monitorization of patients. Radiologic evaluation of diaphragm pillars in T1-weighted imaging axial sequences could also be helpful to predict respiratory insufficiency.

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Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests

Frontiers in Neurology ◽

10.3389/fneur.2021.634766 ◽

2021 ◽

Vol 12 ◽

Author(s):

Claudia Nuñez-Peralta ◽

Paula Montesinos ◽

Alicia Alonso-Jiménez ◽

Jorge Alonso-Pérez ◽

David Reyes-Leiva ◽

...

Keyword(s):

Pompe Disease ◽

Muscle Function ◽

Late Onset ◽

Magnetization Transfer ◽

Intramuscular Fat ◽

Fatty Tissue ◽

Healthy Controls ◽

Function Tests ◽

Fat Fraction ◽

Spearman Test

Objectives: Magnetization transfer (MT) imaging exploits the interaction between bulk water protons and protons contained in macromolecules to induce signal changes through a special radiofrequency pulse. MT detects muscle damage in patients with neuromuscular conditions, such as limb-girdle muscular dystrophies or Charcot-Marie-Tooth disease, which are characterized by progressive fiber loss and replacement by fatty tissue. In Pompe disease, in which there is, in addition, an accumulation of glycogen inside the muscle fibers, MT has not been tested yet. Our aim is to estimate MT ratio (MTR) in the skeletal muscle of these patients and correlate it with intramuscular fat fraction (FF) and results of muscle function tests.Methods: We obtained two-point axial Dixon and Dixon-MT sequences of the right thigh on a 1.5 Teslas MRI scanner in 60 individuals, including 29 late onset Pompe disease patients, 2 patients with McArdle disease, and 29 age and sex matched healthy controls. FF and MTR were estimated. Muscle function using several muscle function tests, including quantification of muscle strength, timed test quality of life scales, conventional spirometry obtaining forced vital capacity while sitting and in the supine position, were assessed in all patients.Results: MTR was significantly lower in Pompe patients compared with controls (45.5 ± 8.5 vs. 51.7 ± 2.3, Student T-test, p < 0.05). There was a negative correlation between the MTR and FF muscles studied (correlation coefficient: −0.65, Spearman test: p < 0.05). MTR correlated with most of the muscle function test results. We analyzed if there was any difference in MTR values between Pompe patients and healthy controls in those muscles that did not have an increase in fat, a measure that could be related to the presence of glycogen in skeletal muscles, but we did not identify significant differences except in the adductor magnus muscle (48.4 ± 3.6 in Pompe vs. 51 ± 1.3 in healthy controls, Student T-test = 0.023).Conclusions: MTR is a sensitive tool to identify muscle loss in patients with Pompe disease and shows a good correlation with muscle function tests. Therefore, the MT technique can be useful in monitoring muscle degeneration in Pompe disease in clinical trials or natural history studies.

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Platelet Derived Growth Factor-AA Correlates With Muscle Function Tests and Quantitative Muscle Magnetic Resonance in Dystrophinopathies

Frontiers in Neurology ◽

10.3389/fneur.2021.659922 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alicia Alonso-Jiménez ◽

Esther Fernández-Simón ◽

Daniel Natera-de Benito ◽

Carlos Ortez ◽

Carme García ◽

...

Keyword(s):

Growth Factors ◽

Growth Factor ◽

Serum Concentration ◽

Muscle Function ◽

Transforming Growth Factor ◽

Tissue Growth ◽

Platelet Derived Growth Factor ◽

Blood Samples ◽

Function Tests ◽

Fat Fraction

Introduction: Duchenne (DMD) and Becker (BMD) muscular dystrophy are X-linked muscular disorders produced by mutations in the DMD gene which encodes the protein dystrophin. Both diseases are characterized by progressive involvement of skeletal, cardiac, and respiratory muscles. As new treatment strategies become available, reliable biomarkers and outcome measures that can monitor disease progression are needed for clinical trials.Methods: We collected clinical and functional data and blood samples from 19 DMD patients, 13 BMD patients, and 66 healthy controls (8 pediatric and 58 adult controls), and blood samples from 15 patients with dysferlinopathy (DYSF) and studied the serum concentration of 4 growth factors involved in the process of muscle fibrosis. We correlated the serum concentration of these growth factors with several muscle function tests, spirometry results and fat fraction identified by quantitative Dixon muscle MRI.Results: We found significant differences in the serum concentration of Platelet Derived Growth Factor-AA (PDGF-AA) between DMD patients and pediatric controls, in Connective Tissue Growth Factor (CTGF) between BMD patients and adult controls, and in and Transforming Growth Factor- β1 (TGF-β1) between BMD and DYSF patients. PDGF-AA showed a good correlation with several muscle function tests for both DMD and BMD patients and with thigh fat fraction in BMD patients. Moreover, PDGF-AA levels were increased in muscle biopsies of patients with DMD and BMD as was demonstrated by immunohistochemistry and Real-Time PCR studies.Conclusion: Our study suggests that PDGF-AA should be further investigated in a larger cohort of DMD and BMD patients because it might be a good biomarker candidate to monitor the progression of these diseases.

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Corrigendum: Magnetization Transfer Ratio in Lower Limbs of Late Onset Pompe Patients Correlates With Intramuscular Fat Fraction and Muscle Function Tests

Frontiers in Neurology ◽

10.3389/fneur.2021.727020 ◽

2021 ◽

Vol 12 ◽

Author(s):

Claudia Nuñez-Peralta ◽

Paula Montesinos ◽

Alicia Alonso-Jiménez ◽

Jorge Alonso-Pérez ◽

David Reyes-Leiva ◽

...

Keyword(s):

Muscle Function ◽

Late Onset ◽

Magnetization Transfer ◽

Intramuscular Fat ◽

Lower Limbs ◽

Magnetization Transfer Ratio ◽

Transfer Ratio ◽

Function Tests ◽

Fat Fraction

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MRI vastus lateralis fat fraction predicts loss of ambulation in Duchenne muscular dystrophy

Neurology ◽

10.1212/wnl.0000000000008939 ◽

2020 ◽

Vol 94 (13) ◽

pp. e1386-e1394 ◽

Cited By ~ 6

Author(s):

Karin J. Naarding ◽

Harmen Reyngoudt ◽

Erik W. van Zwet ◽

Melissa T. Hooijmans ◽

Cuixia Tian ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Predictive Value ◽

Mixed Model ◽

Cox Model ◽

Medical Center ◽

Vastus Lateralis ◽

Hazard Ratio ◽

Quantitative Mri ◽

Fat Fraction

ObjectiveWe studied the potential of quantitative MRI (qMRI) as a surrogate endpoint in Duchenne muscular dystrophy by assessing the additive predictive value of vastus lateralis (VL) fat fraction (FF) to age on loss of ambulation (LoA).MethodsVL FFs were determined on longitudinal Dixon MRI scans from 2 natural history studies in Leiden University Medical Center (LUMC) and Cincinnati Children's Hospital Medical Center (CCHMC). CCHMC included ambulant patients, while LUMC included a mixed ambulant and nonambulant population. We fitted longitudinal VL FF values to a sigmoidal curve using a mixed model with random slope to predict individual trajectories. The additive value of VL FF over age to predict LoA was calculated from a Cox model, yielding a hazard ratio.ResultsEighty-nine MRIs of 19 LUMC and 15 CCHMC patients were included. At similar age, 6-minute walking test distances were smaller and VL FFs were correspondingly higher in LUMC compared to CCHMC patients. Hazard ratio of a percent-point increase in VL FF for the time to LoA was 1.15 for LUMC (95% confidence interval [CI] 1.05–1.26; p = 0.003) and 0.96 for CCHMC (95% CI 0.84–1.10; p = 0.569).ConclusionsThe hazard ratio of 1.15 corresponds to a 4.11-fold increase of the instantaneous risk of LoA in patients with a 10% higher VL FF at any age. Although results should be confirmed in a larger cohort with prospective determination of the clinical endpoint, this added predictive value of VL FF to age on LoA supports the use of qMRI FF as an endpoint or stratification tool in clinical trials.

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Effect of Surgical Alterations of the Tensor Veli Palatini Muscle onc Eustachian Tube Function

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894800890s313 ◽

1980 ◽

Vol 89 (3_suppl) ◽

pp. 47-54 ◽

Cited By ~ 48

Author(s):

Erdem I. Cantekin ◽

David C. Phillips ◽

Charles D. Bluestone ◽

William J. Doyle ◽

Kyle K. Kimes

Keyword(s):

Eustachian Tube ◽

Otitis Media With Effusion ◽

Forced Response ◽

Eustachian Tube Function ◽

Complete Excision ◽

Function Tests ◽

Short Period ◽

Tube Function ◽

Tensor Veli Palatini Muscle ◽

One Year

Previous studies in humans have indicated that functional obstruction of the eustachian tube (ET) is an important factor in the pathogenesis of otitis media with effusion (OME). This type of obstruction appears to be related to the structural properties of the tube, or to an inefficient active tubal opening mechanism, or both. In this study, functional ET obstruction was created in 22 rhesus monkeys ( Macaca mulatta) by surgically altering the tensor veli palatini (TVP) muscle using three different procedures: 1) complete excision of the muscle; 2) transection of the superficial muscle bundle; or 3) transposition of the muscle tendon medial to the hamular process. Prior to surgery, weekly tympanometry, pneumatic otoscopy, and otomicroscopic examinations were performed for a period of at least six months to document middle ear (ME) status. A minimum of four ET function tests were performed on each animal using the inflation-deflation and forced-response tests. Following surgery, these tests and examinations were continued for periods of up to one year. Postoperatively, the animals in which the TVP had been excised developed a sterile ME effusion which proved to be a chronic condition which persisted throughout the follow-up period. Eustachian tube function tests showed a complete absence of any active tubal dilation by swallowing. Animals that had the muscle transected developed abnormal ME pressures, or effusions, or both, which returned to normal in some ears, but which were recurrent or chronic in others. Eustachian tube function tests in these animals showed an initial loss of active tubal function which gradually improved, but not to normal levels, presumably as a result of healing of the muscle. In cases in which the muscle was transposed the ME pathology and ET dysfunction were similar after the surgery, but improved within a short period of time. These data suggest that alteration of the TVP muscle can create functional obstruction of the ET. The severity of ET obstruction depends upon the surgical procedure undertaken. The results of postoperative ET function tests were similar to those recorded from children with recurrent and chronic OME.

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Adenosine-Assisted Management of Intracranial Aneurysm

Journal of Neuroanaesthesiology and Critical Care ◽

10.1055/s-0038-1676555 ◽

2019 ◽

Vol 06 (01) ◽

pp. 013-017

Author(s):

Bhoomika Thakore ◽

Shwetal Goraksha ◽

Joseph N. Monteiro

Keyword(s):

Circulatory Arrest ◽

Cerebral Aneurysms ◽

Rapid Onset ◽

Deep Hypothermic Circulatory Arrest ◽

Suitable Alternative ◽

Ideal Agent ◽

Surgical Clip ◽

Short Period ◽

Low Incidence ◽

Assisted Management

AbstractCerebral aneurysms can be complex and variable in size, position, and morphology, resulting in difficult surgical exposure and secure clip placement. They have a high mortality rate when ruptured, and though endovascular techniques have emerged to tackle this, surgical clip ligation remains the preferred modality for some aneurysms. Various techniques that help the surgeon dissect the aneurysmal dome and apply the clip are temporary clip ligation of proximal vessels, deep hypothermic circulatory arrest, and balloon suction decompression. All of them require significant logistics and result in increased morbidity and mortality. Adenosine is a suitable alternative for inducing a temporary flow arrest, causing a short period of controlled hypotension. Its rapid onset and offset property along with low incidence of adverse events makes it an ideal agent in this regard. We present here a review on its use, contraindications, safety profile, and future applications.

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Serum Scoring and Quantitative Magnetic Resonance Imaging in Intestinal Failure-Associated Liver Disease: A Feasibility Study

Nutrients ◽

10.3390/nu12072151 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2151

Author(s):

Konstantinos C. Fragkos ◽

María Claudia Picasso Bouroncle ◽

Shankar Kumar ◽

Lucy Caselton ◽

Alex Menys ◽

...

Keyword(s):

Liver Disease ◽

Liver Diseases ◽

Liver Blood Flow ◽

Intestinal Failure ◽

Quantitative Mri ◽

Liver Fat ◽

Gamma Glutamyl Transferase ◽

Small Bowel Motility ◽

Fat Fraction ◽

Glutamyl Transferase

(1) Background: Intestinal failure-associated liver disease (IFALD) in adults is characterized by steatosis with variable progression to fibrosis/cirrhosis. Reference standard liver biopsy is not feasible for all patients, but non-invasive serological and quantitative MRI markers for diagnosis/monitoring have not been previously validated. Here, we examine the potential of serum scores and feasibility of quantitative MRI used in non-IFALD liver diseases for the diagnosis of IFALD steatosis; (2) Methods: Clinical and biochemical parameters were used to calculate serum scores in patients on home parenteral nutrition (HPN) with/without IFALD steatosis. A sub-group underwent multiparameter quantitative MRI measurements of liver fat fraction, iron content, tissue T1, liver blood flow and small bowel motility; (3) Results: Compared to non-IFALD (n = 12), patients with IFALD steatosis (n = 8) demonstrated serum score elevations in Enhanced Liver Fibrosis (p = 0.032), Aspartate transaminase-to-Platelet Ratio Index (p < 0.001), Fibrosis-4 Index (p = 0.010), Forns Index (p = 0.001), Gamma-glutamyl transferase-to-Platelet Ratio Index (p = 0.002) and Fibrosis Index (p = 0.001). Quantitative MRI scanning was feasible in all 10 sub-group patients. Median liver fat fraction was higher in IFALD steatosis patients (10.9% vs 2.1%, p = 0.032); other parameter differences were non-significant; (4) Conclusion: Serum scores used for non-IFALD liver diseases may be useful in IFALD steatosis. Multiparameter MRI is feasible in patients on HPN.

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