An advanced magnetic resonance imaging perspective on the etiology of deep tissue injury.

Early diagnosis of deep tissue injury remains problematic due to the complicated and multifactorial nature of damage induction and the many processes involved in damage development and recovery. In this paper, we present a comprehensive assessment of deep tissue injury development and remodeling in a rat model by multiparametric magnetic resonance imaging (MRI) and histopathology. The tibialis anterior muscle of rats was subjected to mechanical deformation for 2 h. Multiparametric in vivo MRI, consisting of T2, T2*, mean diffusivity (MD), and angiography measurements, was applied before, during, and directly after indentation as well as at several time points during a 14-day follow-up. MRI readouts were linked to histological analyses of the damaged tissue. The results showed dynamic change in various MRI parameters, reflecting the histopathological status of the tissue during damage induction and repair. Increased T2 corresponded with edema, muscle cell damage, and inflammation. T2* was related to tissue perfusion, hemorrhage, and inflammation. MD increase and decrease was reported on the tissue's microstructural integrity and reflected muscle degeneration and edema as well as fibrosis. Angiography provided information on blockage of blood flow during deformation. Our results indicate that the effects of a single damage-causing event of only 2 h of deformation were present up to 14 days. The initial tissue response to deformation, as observed by MRI, starts at the edge of the indentation. The quantitative MRI readouts provided distinct and complementary information on the extent, temporal evolution, and microstructural basis of deep tissue injury-related muscle damage. NEW & NOTEWORTHY We have applied a multiparametric MRI approach linked to histopathology to characterize damage development and remodeling in a rat model of deep tissue injury. Our approach provided several relevant insights in deep tissue injury. Response to damage, as observed by MRI, started at some distance from the deformation. Damage after a single indentation period persisted up to 14 days. The MRI parameters provided distinct and complementary information on the microstructural basis of the damage.

A MRI-Compatible Combined Mechanical Loading and MR Elastography Setup to Study Deformation-Induced Skeletal Muscle Damage in Rats.

Deformation of skeletal muscle in the proximity of bony structures may lead to deep tissue injury category of pressure ulcers. Changes in mechanical properties have been proposed as a risk factor in the development of deep tissue injury and may be useful as a diagnostic tool for early detection. MRE allows for the estimation of mechanical properties of soft tissue through analysis of shear wave data. The shear waves originate from vibrations induced by an external actuator placed on the tissue surface. In this study a combined Magnetic Resonance (MR) compatible indentation and MR Elastography (MRE) setup is presented to study mechanical properties associated with deep tissue injury in rats. The proposed setup allows for MRE investigations combined with damage-inducing large strain indentation of the Tibialis Anterior muscle in the rat hind leg inside a small animal MR scanner. An alginate cast allowed proper fixation of the animal leg with anatomical perfect fit, provided boundary condition information for FEA and provided good susceptibility matching. MR Elastography data could be recorded for the Tibialis Anterior muscle prior to, during, and after indentation. A decaying shear wave with an average amplitude of approximately 2 µm propagated in the whole muscle. MRE elastograms representing local tissue shear storage modulus Gd showed significant increased mean values due to damage-inducing indentation (from 4.2 ± 0.1 kPa before to 5.1 ± 0.6 kPa after, p<0.05). The proposed setup enables controlled deformation under MRI-guidance, monitoring of the wound development by MRI, and quantification of tissue mechanical properties by MRE. We expect that improved knowledge of changes in soft tissue mechanical properties due to deep tissue injury, will provide new insights in the etiology of deep tissue injuries, skeletal muscle damage and other related muscle pathologies.

Assessment of Myocardial Fibrosis in Mice Using a T2*-Weighted 3D Radial Magnetic Resonance Imaging Sequence.

BACKGROUND: Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis. OBJECTIVE: To goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart. METHODS: C57BL/6 mice were studied with MI (n = 20, replacement fibrosis), transverse aortic constriction (TAC) (n = 18, diffuse fibrosis), and as control (n = 10). 3D center-out radial T2*-weighted images with varying TE were acquired in vivo and ex vivo (TE = 21 µs-4 ms). Ex vivo T2*-weighted signal decay with TE was analyzed using a 3-component model. Subtraction of short- and long-TE images was used to highlight fibrotic tissue with short T2*. The presence of fibrosis was validated using histology and correlated to MRI findings. RESULTS: Detailed ex vivo T2*-weighted signal analysis revealed a fast (T2*fast), slow (T2*slow) and lipid (T2*lipid) pool. T2*fast remained essentially constant. Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts. T2*slow correlated with the presence of diffuse fibrosis in TAC hearts (r = 0.82, P = 0.01). Ex vivo and in vivo subtraction images depicted a positive contrast in the infarct co-localizing with the scar. Infarct volumes from histology and subtraction images linearly correlated (r = 0.94, P<0.001). Region-of-interest analysis in the in vivo post-MI and TAC hearts revealed significant T2* shortening due to fibrosis, in agreement with the ex vivo results. However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue.

Quantitative first-pass perfusion MRI of the mouse myocardium.

In this article, we present a first-pass perfusion imaging protocol to determine quantitative regional perfusion values (in mL min(-1) g(-1)) of the mouse myocardium. Perfusion was quantified using a Fermi-constrained deconvolution of the myocardial tissue response with the arterial input function. A dual-bolus approach was implemented. Experimental evidence is presented for the linearity of signal intensity in the left-ventricular lumen during the prebolus (r=0.99, P<0.001) and in the myocardium during the full-bolus injection (r=0.99, P<0.01) as function of Gd(DTPA)2- injection concentration used. The prebolus was used to reconstruct a nonsaturated arterial input function. Regional perfusion values proved repeatable in a cohort of nine healthy C57BL/6 mice. The perfusion values over two measurements with a 1-week interval were 7.3±0.9 and 7.2±0.6 mL min(-1) g(-1), respectively. No effects of time (P>0.05) and myocardial region (P>0.05) were observed. The between-session coefficient of variation was only 6%, whereas the inter-animal coefficient of variation was 11 and 8% for the separate experiments. We expect that the first-pass perfusion method here presented will be useful in preclinical studies of myocardial perfusion deficits and valuable to assess the impact of pro-angiogenic therapy after myocardial infarction.

Intersubject differences in the effect of acidosis on phosphocreatine recovery kinetics in muscle after exercise are due to differences in proton efflux rates.

(31)P magnetic resonance spectroscopy provides the possibility of obtaining bioenergetic data during skeletal muscle exercise and recovery. The time constant of phosphocreatine (PCr) recovery (tau(PCr)) has been used as a measure of mitochondrial function. However, cytosolic pH has a strong influence on the kinetics of PCr recovery, and it has been suggested that tau(PCr) should be normalized for end-exercise pH. A general correction can only be applied if there are no intersubject differences in the pH dependence of tau(PCr). We investigated the pH dependence of tau(PCr) on a subject-by-subject basis. Furthermore, we determined the kinetics of proton efflux at the start of recovery. Intracellular acidosis slowed PCr recovery, and the pH dependence of tau(PCr) differed among subjects, ranging from -33.0 to -75.3 s/pH unit. The slope of the relation between tau(PCr) and end-exercise pH was positively correlated with both the proton efflux rate and the apparent proton efflux rate constant, indicating that subjects with a smaller pH dependence of tau(PCr) have a higher proton efflux rate. Our study implies that simply correcting tau(PCr) for end-exercise pH is not adequate, in particular when comparing patients and control subjects, because certain disorders are characterized by altered proton efflux from muscle fibers.

Comparison between prospective and retrospective triggering for mouse cardiac MRI.

High-resolution magnetic resonance imaging (MRI) has evolved into one of the major non-invasive tools to study the healthy and diseased mouse heart. This study presents a Cartesian CINE MRI protocol based on a fast low-angle shot sequence with a navigator echo to generate cardiac triggering and respiratory gating signals retrospectively, making the use of ECG leads and respiratory motion sensors obsolete. MRI of the in vivo mouse heart using this sequence resulted in CINE images with no detectable cardiac and respiratory motion artefacts. The retrospective method allows for steady-state imaging of the mouse heart, which is essential for quantitative contrast-enhanced MRI studies. A comparison was made between prospective and retrospective methods in terms of the signal-to-noise ratio and the contrast-to-noise ratio between blood and myocardial wall, as well as global cardiac functional indices: end-diastolic volume, end-systolic volume, stroke volume and ejection fraction. The retrospective method resulted in almost constant left-ventricle wall signal intensity throughout the cardiac cycle, at the expense of a decrease in the signal-to-noise ratio and the contrast-to-noise ratio between blood and myocardial wall as compared with the prospective method. Prospective and retrospective sequences yielded comparable global cardiac functional indices. The largest mean relative difference found was 8% for the end-systolic volume.