Quantitative muscle MRI as a sensitive marker of early muscle pathology in myotonic dystrophy type 1.

BACKGROUND: Quantitative muscle MRI as a sensitive marker of early muscle pathology and disease progression in adult-onset myotonic dystrophy type 1. The utility of muscle MRI as a marker of muscle pathology and disease progression in adult-onset myotonic dystrophy type 1 (DM1) was evaluated. METHODS: This prospective, longitudinal study included 67 observations from 36 DM1 patients (50% female), and 92 observations from 49 healthy adults (49% female). Lower-leg 3T magnetic resonance imaging (MRI) scans were acquired. Volume and fat fraction (FF) were estimated using a three-point Dixon method, and T2-relaxometry was determined using a multi-echo spin-echo sequence. Muscles were segmented automatically. Mixed linear models were conducted to determine group differences across muscles and image modality, accounting for age, sex, and repeated observations. Differences in rate of change in volume, T2-relaxometry, and FF were also determined with mixed linear regression that included a group by elapsed time interaction. RESULTS: Compared with healthy adults, DM1 patients exhibited reduced volume of the tibialis anterior, soleus, and gastrocnemius (GAS) (all, P < .05). T2-relaxometry and FF were increased across all calf muscles in DM1 compared to controls. (all, P < .01). Signs of muscle pathology, including reduced volume, and increased T2-relaxometry and FF were already noted in DM1 patients who did not exhibit clinical motor symptoms of DM1. As a group, DM1 patients exhibited a more rapid change than did controls in tibialis posterior volume (P = .05) and GAS T2-relaxometry (P = .03) and FF (P = .06). CONCLUSIONS: Muscle MRI renders sensitive, early markers of muscle pathology and disease progression in DM1. T2 relaxometry may be particularly sensitive to early muscle changes related to DM1.

R1ρ sensitivity to pH and other compounds at clinically accessible spin-lock fields in the presence of proteins.

Numerous human diseases involve abnormal metabolism, and proton exchange is an effective source of magnetic resonance imaging (MRI) contrast for assessing metabolism. One MRI technique that capitalizes on proton exchange is R1 relaxation in the rotating frame (R1ρ ). Here, we investigated the sensitivity of R1ρ to various proton-exchange mechanisms at spin-lock pulses within Food and Drug Administration (FDA) safety guidelines for radiofrequency-induced heating. We systematically varied pH known to change the rate of proton exchange as well as the glucose and lysine concentrations, thus changing the number of amide, hydroxyl and amine exchangeable sites in a series of egg-white albumin phantoms. The resulting effects on quantitative relaxation time measurements of R1ρ , R1 and R2 were observed at 3 T. Using spin-lock amplitudes available for human imaging (less than 23.5 µT) at near physiologic temperatures, we found R1ρ was more sensitive to physiologic changes in pH than to changes in glucose and lysine concentrations. In addition, R1ρ was more sensitive to pH changes than R1 and R2 . Models of proton exchange fitted to the relaxation measurements suggest that amide groups were the primary source of pH sensitivity. Together, these experiments suggest an optimal spin-lock amplitude for measuring pH changes while not exceeding FDA-subject heating limitations.

Bone contusion progression from traumatic knee injury: association of rate of contusion resolution with injury severity.

BACKGROUND: Bone contusions are frequently encountered in magnetic resonance imaging (MRI) evaluation of knee anterior cruciate ligament (ACL) injuries. Their role as indicators of injury severity remains unclear, primarily due to indeterminate levels of joint injury forces and to a lack of preinjury imaging. PURPOSE: The purpose of this study was to 1) quantify bone contusion pathogenesis following traumatic joint injuries using fixed imaging follow-ups, and 2) assess the feasibility of using longitudinal bone contusion volumes as an indicator of knee injury severity. STUDY DESIGN: Prospective sequential MRI follow-ups of a goat cohort exposed to controlled stifle trauma in vivo were compared to parallel clinical MRI follow-ups of a human ACL tear patient series. METHODS: Reproducible cartilage impact damage of various energy magnitudes was applied in a survival goat model, coupled with partial resection of anterior portions of medial menisci. Both emulate injury patterns to the knee osteochondral structures commonly encountered in human ACL injury imaging as well as instability from resultant ligament laxity. Longitudinal clinical MRI sequences portrayed stifle bone contusion evolution through 6 months after the inciting event. RESULTS: In the first 2 weeks, biological response variability dominated the whole-joint response with no apparent correlation to trauma severity. Control goats subjected to partial meniscectomy alone exhibited minimal bone response. Thereafter, 0.6 J impact bone contusions portrayed a faster rate of resolution than those induced by 1.2 J cartilage impacts. CONCLUSION: Bone contusion sizes combined with time of persistence are likely better measures of joint injury severity than isolated bone contusion volume.

Haploinsufficiency of interferon regulatory factor 6 alters brain morphology in the mouse.

Orofacial clefts are among the commonest birth defects. Among many genetic contributors to orofacial clefting, Interferon Regulatory Factor 6 (IRF6) is unique since mutations in this gene cause Van der Woude (VWS), the most common clefting syndrome. Furthermore, variants in IRF6 contribute to increased risk for non-syndromic cleft lip and/or palate (NSCL/P). Our previous work shows that individuals with either VWS or NSCL/P may have cerebral anomalies (larger anterior, smaller posterior regions), and a smaller cerebellum. The objective of this study was to test the hypothesis that disrupting Irf6 in the mouse will result in quantitative brain changes similar to those reported for humans with VWS and NSCL/P. Male mice heterozygous for Irf6 (Irf6(gt1/+); n = 9) and wild-type (Irf6(+/+) ; n = 6) mice at comparable age underwent a 4.7-T MRI scan to obtain quantitative measures of cortical and subcortical brain structures. There was no difference in total brain volume between groups. However, the frontal cortex was enlarged in the Irf6(gt1/+) mice compared to that of wild types (P = 0.028) while the posterior cortex did not differ. In addition, the volume of the cerebellum of Irf6(gt1/+) mice was decreased (P = 0.004). Mice that were heterozygous for Irf6 showed a similar pattern of brain anomalies previously reported in humans with VWS and NSCL/P. These structural differences were present in the absence of overt oral clefts. These results support a role for IRF6 in brain morphometry and provide evidence for a potential genetic link to abnormal brain development in orofacial clefting.

Double-bundle ACL reconstruction: novice surgeons utilizing computer-assisted navigation versus experienced surgeons.

PURPOSE: Anatomic double-bundle ACL reconstruction presents a unique technical challenge for surgeons, requiring precise placement of multiple tunnels in a relatively small area. As the necessity of anatomic reconstruction has been stressed throughout the literature, developing a method to consistently improve the accuracy and precision of tunnel placement is essential. We aimed to investigate whether computer-assisted navigation allows novice surgeons to place double-bundle ACL tunnels with a similar degree of accuracy to experienced surgeons operating without computer assistance. METHODS: A novice surgeon group comprising three medical students performed double-bundle ACL reconstruction using passive computer-assisted navigation in 11 cadaver knees. Their individual results were compared to those of three experienced orthopaedic surgeons, each performing the identical procedure without the use of computer-assisted navigation in 9 cadaver knees. RESULTS AND CONCLUSION: There were no significant differences in placement of either the AM or PL tunnels on the tibial plateau between the novice surgeons using computer-assisted navigation and the experienced surgeons. However, on the lateral femoral condyle, the novice surgeons placed the AM and PL tunnels significantly more anterior along Blumensaat's line, on average, compared to the experienced surgeons.