The relationship between the diaphragm thickening fraction and the transdiaphragmatic pressure, the reference method to evaluate the diaphragm function, has not been clearly established. This study ...investigated the global and intraindividual relationship between the thickening fraction of the diaphragm and the transdiaphragmatic pressure. The authors hypothesized that the diaphragm thickening fraction would be positively and significantly correlated to the transdiaphragmatic pressure, in both healthy participants and ventilated patients.
Fourteen healthy individuals and 25 mechanically ventilated patients (enrolled in two previous physiologic investigations) participated in the current study. The zone of apposition of the right hemidiaphragm was imaged simultaneously to transdiaphragmatic pressure recording within different breathing conditions, i.e., external inspiratory threshold loading in healthy individuals and various pressure support settings in patients. A blinded offline breath-by-breath analysis synchronously computed the changes in transdiaphragmatic pressure, the diaphragm pressure-time product, and diaphragm thickening fraction. Global and intraindividual relationships between variables were assessed.
In healthy subjects, both changes in transdiaphragmatic pressure and diaphragm pressure-time product were moderately correlated to diaphragm thickening fraction (repeated measures correlation = 0.40, P < 0.0001; and repeated measures correlation = 0.38, P < 0.0001, respectively). In mechanically ventilated patients, changes in transdiaphragmatic pressure and thickening fraction were weakly correlated (repeated measures correlation = 0.11, P = 0.008), while diaphragm pressure-time product and thickening fraction were not (repeated measures correlation = 0.04, P = 0.396). Individually, changes in transdiaphragmatic pressure and thickening fraction were significantly correlated in 8 of 14 healthy subjects (ρ = 0.30 to 0.85, all P < 0.05) and in 2 of 25 mechanically ventilated patients (ρ = 0.47 to 0.64, all P < 0.05). Diaphragm pressure-time product and thickening fraction correlated in 8 of 14 healthy subjects (ρ = 0.41 to 0.82, all P < 0.02) and in 2 of 25 mechanically ventilated patients (ρ = 0.63 to 0.66, all P < 0.01).
Overall, diaphragm function as assessed with transdiaphragmatic pressure was weakly related to diaphragm thickening fraction. The diaphragm thickening fraction should not be used in healthy subjects or ventilated patients when changes in diaphragm function are evaluated.
Although idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases nearly all patients display muscle inflammation. Originally, muscle biopsy was considered as the gold standard ...for IIM diagnosis. The development of muscle imaging led to revisiting not only the IIM diagnosis strategy but also the patients’ follow‐up. Different techniques have been tested or are in development for IIM including positron emission tomography, ultrasound imaging, ultrasound shear wave elastography, though magnetic resonance imaging (MRI) remains the most widely used technique in routine. Whereas guidelines on muscle imaging in myositis are lacking here we reviewed the relevance of muscle imaging for both diagnosis and myositis patients’ follow‐up. We propose recommendations about when and how to perform MRI on myositis patients, and we describe new techniques that are under development.
Muscle imaging and especially muscle MRI is a powerful technique for both IIM diagnosis and follow‐up. Muscle MRI is actually the best muscle imaging technique in routine, and it is widely used, but guidelines determining when and how to use it in myositis patients are lacking.
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, T
, 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.
Greater diaphragm fatigue has been reported after hypoxic versus normoxic exercise, but whether this is due to increased ventilation and therefore work of breathing or reduced blood oxygenation per ...se remains unclear. Hence, we assessed the effect of different blood oxygenation level on isolated hyperpnoea-induced inspiratory and expiratory muscle fatigue.
Twelve healthy males performed three 15-min isocapnic hyperpnoea tests (85% of maximum voluntary ventilation with controlled breathing pattern) in normoxic, hypoxic (SpO2 = 80%) and hyperoxic (FiO2 = 0.60) conditions, in a random order. Before, immediately after and 30 min after hyperpnoea, transdiaphragmatic pressure (P(di,tw)) was measured during cervical magnetic stimulation to assess diaphragm contractility, and gastric pressure (P(ga,tw)) was measured during thoracic magnetic stimulation to assess abdominal muscle contractility. Two-way analysis of variance (time x condition) was used to compare hyperpnoea-induced respiratory muscle fatigue between conditions.
Hypoxia enhanced hyperpnoea-induced P(di,tw) and P(ga,tw) reductions both immediately after hyperpnoea (P(di,tw) : normoxia -22 +/- 7% vs hypoxia -34 +/- 8% vs hyperoxia -21 +/- 8%; P(ga,tw) : normoxia -17 +/- 7% vs hypoxia -26 +/- 10% vs hyperoxia -16 +/- 11%; all P < 0.05) and after 30 min of recovery (P(di,tw) : normoxia -10 +/- 7% vs hypoxia -16 +/- 8% vs hyperoxia -8 +/- 7%; P(ga,tw) : normoxia -13 +/- 6% vs hypoxia -21 +/- 9% vs hyperoxia -12 +/- 12%; all P < 0.05). No significant difference in (di,tw) or P(ga,tw) reductions was observed between normoxic and hyperoxic conditions. Also, heart rate and blood lactate concentration during hyperpnoea were higher in hypoxia compared to normoxia and hyperoxia.
These results demonstrate that hypoxia exacerbates both diaphragm and abdominal muscle fatigability. These results emphasize the potential role of respiratory muscle fatigue in exercise performance limitation under conditions coupling increased work of breathing and reduced O2 transport as during exercise in altitude or in hypoxemic patients.
Abstract
Background
Diaphragm dysfunction is highly prevalent in mechanically ventilated patients. Recent work showed that changes in diaphragm shear modulus (ΔSMdi) assessed using ultrasound shear ...wave elastography (SWE) are strongly related to changes in Pdi (ΔPdi) in healthy subjects. The aims of this study were to investigate the relationship between ΔSMdi and ΔPdi in mechanically ventilated patients, and whether ΔSMdi is responsive to change in respiratory load when varying the ventilator settings.
Methods
A prospective, monocentric study was conducted in a 15-bed ICU. Patients were included if they met the readiness-to-wean criteria. Pdi was continuously monitored using a double-balloon feeding catheter orally introduced. The zone of apposition of the right hemidiaphragm was imaged using a linear transducer (SL10-2, Aixplorer, Supersonic Imagine, France). Ultrasound recordings were performed under various pressure support settings and during a spontaneous breathing trial (SBT). A breath-by-breath analysis was performed, allowing the direct comparison between ΔPdi and ΔSMdi. Pearson’s correlation coefficients (
r
) were used to investigate within-individual relationships between variables, and repeated measure correlations (
R
) were used for determining overall relationships between variables. Linear mixed models were used to compare breathing indices across the conditions of ventilation.
Results
Thirty patients were included and 930 respiratory cycles were analyzed. Twenty-five were considered for the analysis. A significant correlation was found between ΔPdi and ΔSMdi (
R
= 0.45, 95% CIs 0.35 0.54,
p
< 0.001). Individual correlation displays a significant correlation in 8 patients out of 25 (
r
= 0.55–0.86, all
p
< 0.05, versus
r
= − 0.43–0.52, all
p
> 0.06). Changing the condition of ventilation similarly affected ΔPdi and ΔSMdi. Patients in which ΔPdi–ΔSMdi correlation was non-significant had a faster respiratory rate as compared to that of patient with a significant ΔPdi–ΔSMdi relationship (median (Q1–Q3), 25 (18–33) vs. 21 (15–26) breaths.min
−1
, respectively).
Conclusions
We demonstrate that ultrasound SWE may be a promising surrogate to Pdi in mechanically ventilated patients. Respiratory rate appears to negatively impact SMdi measurement. Technological developments are needed to generalize this method in tachypneic patients.
Trial registration
NCT03832231
.
Exercise intolerance in COPD seems to combine abnormal ventilatory mechanics, impaired O2 transport and skeletal muscle dysfunction. However their relative contribution and their influence on ...symptoms reported by patients remain to be clarified. In order to clarify the complex interaction between ventilatory and neuromuscular exercise limiting factors and symptoms, we evaluated respiratory muscles and quadriceps contractile fatigue, dynamic hyperinflation and symptoms induced by exhaustive high-intensity cycling in COPD patients. Fifteen gold II-III COPD patients (age = 67 ± 6 yr; BMI = 26.6 ± 4.2 kg.m(-2)) performed constant-load cycling test at 80% of their peak workload until exhaustion (9.3 ± 2.4 min). Before exercise and at exhaustion, potentiated twitch quadriceps strength (Q(tw)), transdiaphragmatic (P(di,tw)) and gastric (P(ga,tw)) pressures were evoked by femoral nerve, cervical and thoracic magnetic stimulation, respectively. Changes in operational lung volumes during exercise were assessed via repetitive inspiratory capacity (IC) measurements. Dyspnoea and leg discomfort were measured on visual analog scale. At exhaustion, Q(tw) (-33 ± 15%, >15% reduction observed in all patients but two) and Pdi,tw (-20 ± 15%, >15% reduction in 6 patients) were significantly reduced (P<0.05) but not Pga,tw (-6 ± 10%, >15% reduction in 3 patients). Percentage reduction in Q(tw) correlated with the percentage reduction in P(di,tw) (r = 0.66; P<0.05). Percentage reductions in P(di,tw) and P(ga,tw) negatively correlated with the reduction in IC at exhaustion (r = -0.56 and r = -0.62, respectively; P<0.05). Neither dyspnea nor leg discomfort correlated with the amount of muscle fatigue. In conclusion, high-intensity exercise induces quadriceps, diaphragm and less frequently abdominal contractile fatigue in this group of COPD patients. In addition, the rise in end-expiratory lung volume and diaphragm flattening associated with dynamic hyperinflation in COPD might limit the development of abdominal and diaphragm muscle fatigue. This study underlines that both respiratory and quadriceps fatigue should be considered to understand the complex interplay of factors leading to exercise intolerance in COPD patients.
Background
Finding sensitive clinical outcome measures has become crucial in natural history studies and therapeutic trials of neuromuscular disorders. Here, we focus on 1‐year longitudinal data from ...quantitative magnetic resonance imaging (MRI) and phosphorus magnetic resonance spectroscopy (31P MRS) in a placebo‐controlled study of sirolimus for inclusion body myositis (IBM), also examining their links to functional, strength, and clinical parameters in lower limb muscles.
Methods
Quantitative MRI and 31P MRS data were collected at 3 T from a single site, involving 44 patients (22 on placebo, 22 on sirolimus) at baseline and year‐1, and 21 healthy controls. Assessments included fat fraction (FF), contractile cross‐sectional area (cCSA), and water T2 in global leg and thigh segments, muscle groups, individual muscles, as well as 31P MRS indices in quadriceps or triceps surae. Analyses covered patient‐control comparisons, annual change assessments via standard t‐tests and linear mixed models, calculation of standardized response means (SRM), and exploration of correlations between MRI, 31P MRS, functional, strength, and clinical parameters.
Results
The quadriceps and gastrocnemius medialis muscles had the highest FF values, displaying notable heterogeneity and asymmetry, particularly in the quadriceps. In the placebo group, the median 1‐year FF increase in the quadriceps was 3.2% (P < 0.001), whereas in the sirolimus group, it was 0.7% (P = 0.033). Both groups experienced a significant decrease in cCSA in the quadriceps after 1 year (P < 0.001), with median changes of 12.6% for the placebo group and 5.5% for the sirolimus group. Differences in FF and cCSA changes between the two groups were significant (P < 0.001). SRM values for FF and cCSA were 1.3 and 1.4 in the placebo group and 0.5 and 0.8 in the sirolimus group, respectively. Water T2 values were highest in the quadriceps muscles of both groups, significantly exceeding control values in both groups (P < 0.001) and were higher in the placebo group than in the sirolimus group. After treatment, water T2 increased significantly only in the sirolimus group's quadriceps (P < 0.01). Multiple 31P MRS indices were abnormal in patients compared to controls and remained unchanged after treatment. Significant correlations were identified between baseline water T2 and FF at baseline and the change in FF (P < 0.001). Additionally, significant correlations were observed between FF, cCSA, water T2, and functional and strength outcome measures.
Conclusions
This study has demonstrated that quantitative MRI/31P MRS can discern measurable differences between placebo and sirolimus‐treated IBM patients, offering promise for future therapeutic trials in idiopathic inflammatory myopathies such as IBM.
Background
The availability of non‐invasive, accessible, and reliable methods for estimating regional skeletal muscle volume is paramount in conditions involving primary and/or secondary muscle ...wasting. This work aimed at (i) optimizing serial bioelectrical impedance analysis (SBIA) by computing a conductivity constant based on quantitative magnetic resonance imaging (MRI) data and (ii) investigating the potential of SBIA for estimating lean regional thigh muscle volume in patients with severe muscle disorders.
Methods
Twenty healthy participants with variable body mass index and 20 patients with idiopathic inflammatory myopathies underwent quantitative MRI. Anatomical images and fat fraction maps were acquired in thighs. After manual muscle segmentation, lean thigh muscle volume (lVMRI) was computed. Subsequently, multifrequency (50 to 350 kHz) serial resistance profiles were acquired between current skin electrodes (i.e. ankle and hand) and voltage electrodes placed on the anterior thigh. In vivo values of the muscle electrical conductivity constant were computed using data from SBIA and MRI gathered in the right thigh of 10 healthy participants. Lean muscle volume (lVBIA) was derived from SBIA measurements using this newly computed constant. Between‐day reproducibility of lVBIA was studied in six healthy participants.
Results
Electrical conductivity constant values ranged from 0.82 S/m at 50 kHz to 1.16 S/m at 350 kHz. The absolute percentage difference between lVBIA and lVMRI was greater at frequencies >270 kHz (P < 0.0001). The standard error of measurement and the intra‐class correlation coefficient for lVBIA computed from measurements performed at 155 kHz (i.e. frequency with minimal difference) against lVMRI were 6.1% and 0.95 in healthy participants and 9.4% and 0.93 in patients, respectively. Between‐day reproducibility of lVBIA was as follows: standard error of measurement = 4.6% (95% confidence interval 3.2, 7.8 %), intra‐class correlation coefficient = 0.98 (95% confidence interval 0.95, 0.99).
Conclusions
These findings demonstrate a strong agreement of lean muscle volume estimated using SBIA against quantitative MRI in humans, including in patients with severe muscle wasting and fatty degeneration. SBIA shows promises for non‐invasive, fast, and accessible estimation and follow‐up of lean regional skeletal muscle volume for transversal and longitudinal studies.
Positive end-expiratory pressure (PEEP) is commonly used in critical care medicine to improve gas exchange. Altitude sickness is associated with exaggerated reduction in arterial oxygenation. We ...assessed the effect of PEEP and pursed lips breathing (PLB) on arterial and tissue oxygenation under normobaric and hypobaric hypoxic conditions.
Sixteen healthy volunteers were exposed to acute normobaric hypoxia (Laboratory study, FiO₂=0.12). The protocol consisted in 3-min phases with PEEPs of 0, 5 or 10 cmH₂O, PLB or similar ventilation than with PEEP-10, interspaced with 3-min phases of free breathing. Arterial (pulse oximetry) and quadriceps (near-infrared spectroscopy) oxygenation, ventilation, cardiac function, esophageal and gastric pressures and subjects' subjective perceptions were recorded continuously. In addition, the effect of PEEP on arterial oxygenation was tested at 4,350 m of altitude in 9 volunteers breathing for 20 min with PEEP-10 (Field study).
During the laboratory study, PEEP-10 increased arterial and quadriceps oxygenation (arterial oxygen saturation +5.6±5.0% and quadriceps oxyhemoglobin +58±73 µmol.cm compared to free breathing; p<0.05). Conversely, PLB did not increase oxygenation. Oxygenation improvement with PEEP-10 was accompanied by an increase in expiratory esophageal and gastric pressures (esophageal pressure swing +5.4±3.2 cmH₂O, p<0.05) but no change in minute ventilation, breathing pattern, end-tidal CO₂ or cardiac function (all p>0.05) compared to PEEP-0. During the field study, PEEP-10 increased arterial oxygen saturation by +6.7±6.0% after the 3(rd) minute with PEEP-10 without further significant increase until the 20(th) minute with PEEP-10. Subjects did not report any significant discomfort with PEEP.
These data indicate that 10-cmH₂O PEEP significantly improves arterial and muscle oxygenation under both normobaric and hypobaric hypoxic conditions in healthy subjects. PEEP-10 could be an attractive non-pharmacological tool to limit blood oxygen desaturation and possibly symptoms at altitude.