RESUMO
Microdamage accumulated through sustained periods of cyclic loading or single overloading events contributes to bone fragility through a reduction in stiffness and strength. Monitoring microdamage in vivo remains unattainable by clinical imaging modalities. As such, there are no established computational methods for clinical fracture risk assessment that account for microdamage that exists in vivo at any specific timepoint. We propose a method that combines multiple clinical imaging modalities to identify an indicative surrogate, which we term 'hidden porosity', that incorporates pre-existing bone microdamage in vivo. To do so, we use the third metacarpal bone of the equine athlete as an exemplary model for fatigue induced microdamage, which coalesces in the subchondral bone. N = 10 metacarpals were scanned by clinical quantitative computed tomography (QCT) and magnetic resonance imaging (MRI). We used a patch-based similarity method to quantify the signal intensity of a fluid sensitive MRI sequence in bone regions where microdamage coalesces. The method generated MRI-derived pseudoCT images which were then used to determine a pre-existing damage (Dpex) variable to quantify the proposed surrogate and which we incorporate into a nonlinear constitutive model for bone tissue. The minimum, median, and maximum detected Dpex of 0.059, 0.209, and 0.353 reduced material stiffness by 5.9%, 20.9%, and 35.3% as well as yield stress by 5.9%, 20.3%, and 35.3%. Limb-specific voxel-based finite element meshes were equipped with the updated material model. Lateral and medial condyles of each metacarpal were loaded to simulate physiological joint loading during gallop. The degree of detected Dpex correlated with a relative reduction in both condylar stiffness (p = 0.001, R2 > 0.74) and strength (p < 0.001, R2 > 0.80). Our results illustrate the complementary value of looking beyond clinical CT, which neglects the inclusion of microdamage due to partial volume effects. As we use clinically available imaging techniques, our results may aid research beyond the equine model on fracture risk assessment in human diseases such as osteoarthritis, bone cancer, or osteoporosis.
RESUMO
OBJECTIVE: In a proof-of-concept study, to quantify myocardial viability in patients with acute myocardial infarction using manganese-enhanced MRI (MEMRI), a measure of intracellular calcium handling. METHODS: Healthy volunteers (n=20) and patients with ST-elevation myocardial infarction (n=20) underwent late gadolinium enhancement (LGE) using gadobutrol and MEMRI using manganese dipyridoxyl diphosphate. Patients were scanned ≤7 days after reperfusion and rescanned after 3 months. Differential manganese uptake was described using a two-compartment model. RESULTS: After manganese administration, healthy control and remote non-infarcted myocardium showed a sustained 25% reduction in T1 values (mean reductions, 288±34 and 281±12 ms). Infarcted myocardium demonstrated less T1 shortening than healthy control or remote myocardium (1157±74 vs 859±36 and 835±28 ms; both p<0.0001) with intermediate T1 values (1007±31 ms) in peri-infarct regions. Compared with LGE, MEMRI was more sensitive in detecting dysfunctional myocardium (dysfunctional fraction 40.5±11.9 vs 34.9%±13.9%; p=0.02) and tracked more closely with abnormal wall motion (r2=0.72 vs 0.55; p<0.0001). Kinetic modelling showed reduced myocardial manganese influx between remote, peri-infarct and infarct regions, enabling absolute discrimination of infarcted myocardium. After 3 months, manganese uptake increased in peri-infarct regions (16.5±3.5 vs 22.8±3.5 mL/100 g/min, p<0.0001), but not the remote (23.3±2.8 vs 23.0±3.2 mL/100 g/min, p=0.8) or infarcted (11.5±3.7 vs 14.0±1.2 mL/100 g/min, p>0.1) myocardium. CONCLUSIONS: Through visualisation of intracellular calcium handling, MEMRI accurately differentiates infarcted, stunned and viable myocardium, and correlates with myocardial dysfunction better than LGE. MEMRI holds major promise in directly assessing myocardial viability, function and calcium handling across a range of cardiac diseases. TRIAL REGISTRATION NUMBERS: NCT03607669; EudraCT number 2016-003782-25.