Differential Laminar Activation Dissociates Encoding and Retrieval in the Human Medial and Lateral Entorhinal Cortex.

The hierarchically organized structures of the medial temporal lobe are critically important for episodic memory function. Accumulating evidence suggests dissociable information processing pathways are maintained throughout these structures including in the medial and lateral entorhinal cortex. Cortical layers provide an additional dimension of dissociation as the primary input to the hippocampus derives from layer 2 neurons in the entorhinal cortex, whereas the deeper layers primarily receive output from the hippocampus. Here, novel high-resolution T2-prepared functional MRI methods were successfully used to mitigate susceptibility artifacts typically affecting MRI signals in this region providing uniform sensitivity across the medial and lateral entorhinal cortex. During the performance of a memory task, healthy human subjects (age 25-33 years, mean age 28.2 ± 3.3 years, 4 female) showed differential functional activation in the superficial and deep layers of the entorhinal cortex associated with task-related encoding and retrieval conditions, respectively. The methods provided here offer an approach to probe layer-specific activation in normal cognition and conditions contributing to memory impairment.SIGNIFICANCE STATEMENT This study provides new evidence for differential neuronal activation in the superficial versus deep layers of the entorhinal cortex associated with encoding and retrieval memory processes, respectively, in cognitively normal adults. The study further shows that this dissociation can be observed in both the medial and the lateral entorhinal cortex. The study was achieved by using a novel functional MRI method allowing us to measure robust functional MRI signals in both the medial and lateral entorhinal cortex that was not possible in previous studies. The methodology established here in healthy human subjects lays a solid foundation for subsequent studies investigating layer-specific and region-specific changes in the entorhinal cortex associated with memory impairment in various conditions such as Alzheimer's disease.

On the optimization of 3D inflow-based vascular-space-occupancy (iVASO) MRI for the quantification of arterial cerebral blood volume (CBVa).

PURPOSE: The inflow-based vascular-space-occupancy (iVASO) MRI was originally developed in a single-slice mode to measure arterial cerebral blood volume (CBVa). When vascular crushers are applied in iVASO, the signals can be sensitized predominantly to small pial arteries and arterioles. The purpose of this study is to perform a systematic optimization and evaluation of a 3D iVASO sequence on both 3 T and 7 T for the quantification of CBVa values in the human brain. METHODS: Three sets of experiments were performed in three separate cohorts. (1) 3D iVASO MRI protocols were compared to single-slice iVASO, and the reproducibility of whole-brain 3D iVASO MRI was evaluated. (2) The effects from different vascular crushers in iVASO were assessed. (3) 3D iVASO MRI results were evaluated in arterial and venous blood vessels identified using ultrasmall-superparamagnetic-iron-oxides-enhanced MRI to validate its arterial origin. RESULTS: 3D iVASO scans showed signal-to-noise ratio (SNR) and CBVa measures consistent with single-slice iVASO with reasonable intrasubject reproducibility. Among the iVASO scans performed with different vascular crushers, the whole-brain 3D iVASO scan with a motion-sensitized-driven-equilibrium preparation with two binomial refocusing pulses and an effective TE of 50 ms showed the best suppression of macrovascular signals, with a relatively low specific absorption rate. When no vascular crusher was applied, the CBVa maps from 3D iVASO scans showed large CBVa values in arterial vessels but well-suppressed signals in venous vessels. CONCLUSION: A whole-brain 3D iVASO MRI scan was optimized for CBVa measurement in the human brain. When only microvascular signals are desired, a motion-sensitized-driven-equilibrium-based vascular crusher with binomial refocusing pulses can be applied in 3D iVASO.

Is Dual Semitendinosus Allograft Stronger Than Turndown for Achilles Tendon Reconstruction? An In Vitro Analysis.

BACKGROUND: Large Achilles tendon defects pose a treatment challenge. The standard treatment with a turndown flap requires a large extensile incision, puts the sural nerve at risk, and demands slow, careful rehabilitation. Dual allograft semitendinosus reconstruction is a new clinical alternative that has the theoretical advantages of a smaller incision, less dissection, and a stronger construct that may allow for faster rehabilitation. QUESTIONS/PURPOSES: In a cadaver biomechanical model, we compared the dual allograft semitendinosus reconstruction with the myofascial turndown in terms of (1) mechanical strength and resistance to deformation and (2) failure mechanisms in reconstruction of large segmental Achilles defects. METHODS: An 8-cm segmental Achilles defect was created in 18 cadaveric lower extremities, nine matched pairs without defect or previous surgery (mean age, 78.4 years; range, 60-97 years; three female and six male pairs). Femoral neck densitometry to determine bone mineral density found that all specimens except two were osteopenic or osteoporotic. Specimens in each pair were assigned to allograft or turndown reconstruction. The constructs were mounted on a load frame and differential variable reluctance transducers were applied to measure deformation. Specimens were preconditioned and then loaded axially. Tensile force and proximal and distal construct deformation were measured at clinical failure, defined as 10 mm of displacement, and at ultimate failure, defined as failure of the reconstruction. Failure mechanism was recorded. RESULTS: Tensile strength at time zero was higher in the allograft versus the turndown construct at clinical failure (156.9 ± 29.7 N versus 107.2 ± 20.0 N, respectively; mean difference, -49.7 N; 95% CI, -66.3 to -33.0 N; p < 0.001) and at ultimate failure (290.9 ± 83.2 N versus 140.7 ± 43.5 N, respectively; mean difference, -150.2 N; 95% CI, -202.9 to -97.6 N; p < 0.001). Distal construct deformation was lower in the turndown versus the allograft construct at clinical failure (1.6 ± 1.0 mm versus 4.7 ± 0.7 mm medially and 2.2 ± 1.0 mm versus 4.8 ± 1.1 mm laterally; p < 0.001). Semitendinosus allograft failure occurred via calcaneal bone bridge fracture in eight of nine specimens. All myofascial turndowns failed via suture pullout through the fascial tissue at its insertion. CONCLUSION: In this comparative biomechanical study, dual semitendinosus allograft reconstruction showed greater tensile strength and construct deformation compared with myofascial turndown in a cadaveric model of large Achilles tendon defects. CLINICAL RELEVANCE: Further study of dual semitendinosus allograft for treatment of severe Achilles tendon defects with cyclic loading and investigation of clinical results will better elucidate the clinical utility and indications for this technique.

Fixation of Regan-Morrey Type II Coronoid Fractures: A Comparison of Screws and Suture Lasso Technique for Resistance to Displacement.

PURPOSE: The aim of this study was to compare the load to failure and stiffness achieved in coronoid fractures treated with a posterior-to-anterior screw versus a suture lasso technique. METHODS: We performed a biomechanical study using 10 pairs of fresh-frozen cadaveric elbows. A transverse osteotomy at the midpoint of the coronoid height was created to simulate a Regan-Morrey type II coronoid fracture. The specimens were randomized to screw fixation or suture lasso fixation. The load to failure and stiffness were then measured using a materials testing machine. RESULTS: Screw fixation provided greater strength and stiffness than suture lasso fixation. Mean load to failure was 405 N in the screw fixation group compared with a load to failure of 207 N for suture fixation. Screw fixation resulted in a mean stiffness of 284 kPa/mm compared with 119 kPa/mm after suture fixation. CONCLUSIONS: Screw fixation was biomechanically superior to fixation using a suture lasso technique. For coronoid fractures in which screw or suture fixation is feasible, screw fixation may provide greater resistance to displacement of the coronoid compared with a suture lasso technique. CLINICAL RELEVANCE: Clinical studies have reported a higher rate of failure after screw fixation compared with suture lasso fixation; however, this study demonstrated a greater stiffness and load to failure after screw fixation of type II coronoid fractures. Screw fixation may provide a stronger fixation construct for fractures of adequate size to support a screw. Further studies may be warranted to assess the importance of securing the anterior capsule to the coronoid tip when using a suture lasso construct because this may affect the stability of the elbow after fixation.

Evaluation of T2-prepared blood oxygenation level dependent functional magnetic resonance imaging with an event-related task: Hemodynamic response function and reproducibility.

T2-prepared (T2prep) blood oxygenation level dependent (BOLD) functional MRI (fMRI) is an alternative fMRI approach developed to mitigate the susceptibility artifacts that are typically observed in brain regions near air-filled cavities, bleeding and calcification, and metallic objects in echo-planar-imaging (EPI) based fMRI images. Here, T2prep BOLD fMRI was evaluated in an event-related paradigm for the first time. Functional experiments were performed using gradient-echo (GRE) EPI, spin-echo (SE) EPI, and T2prep BOLD fMRI during an event-related visual task in 10 healthy human subjects. Each fMRI method was performed with a low (3.4 × 3.4 × 4 mm3) and a high (1.5 mm isotropic) spatial resolution on 3T and a high resolution (1.5 mm isotropic) on 7T. Robust activation were detected in the visual cortex with all three fMRI methods. In each group of fMRI scans (3T low resolution, 3T high resolution, and 7T high resolution), GRE EPI showed the highest signal change (ΔS/S), largest full-width-at-half-maximum (FWHM) and longest time-to-peak (TTP) extracted from the hemodynamic response functions (HRF), indicating substantial signal contribution from large draining veins which have longer response times than microvessels. In contrast, T2prep BOLD showed the lowest ΔS/S, smallest FWHM, and shortest TTP, suggesting that T2prep BOLD may have a purer T2-weighted BOLD contrast that is more sensitive to microvessels compared to GRE/SE EPI BOLD. This trend was more obvious in fMRI scans performed with a lower spatial resolution on a lower field (3T with a 3.4 × 3.4 × 4 mm3 voxel). Scan-rescan reproducibility in the same subjects was comparable among the three fMRI methods. The results from the current study are expected to be useful to establish T2prep BOLD as a useful alternative fMRI approach for event-related fMRI in brain regions with large susceptibility artifacts.

Functional Activities Detected in the Olfactory Bulb and Associated Olfactory Regions in the Human Brain Using T2-Prepared BOLD Functional MRI at 7T.

Olfaction is a fundamental sense that plays a vital role in daily life in humans, and can be altered in neuropsychiatric and neurodegenerative diseases. Blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) using conventional echo-planar-imaging (EPI) based sequences can be challenging in brain regions important for olfactory processing, such as the olfactory bulb (OB) and orbitofrontal cortex, mainly due to the signal dropout and distortion artifacts caused by large susceptibility effects from the sinonasal cavity and temporal bone. To date, few studies have demonstrated successful fMRI in the OB in humans. T2-prepared (T2prep) BOLD fMRI is an alternative approach developed especially for performing fMRI in regions affected by large susceptibility artifacts. The purpose of this technical study is to evaluate T2prep BOLD fMRI for olfactory functional experiments in humans. Olfactory fMRI scans were performed on 7T in 14 healthy participants. T2prep BOLD showed greater sensitivity than GRE EPI BOLD in the OB, orbitofrontal cortex and the temporal pole. Functional activation was detected using T2prep BOLD in the OB and associated olfactory regions. Habituation effects and a bi-phasic pattern of fMRI signal changes during olfactory stimulation were observed in all regions. Both positively and negatively activated regions were observed during olfactory stimulation. These signal characteristics are generally consistent with literature and showed a good intra-subject reproducibility comparable to previous human BOLD fMRI studies. In conclusion, the methodology demonstrated in this study holds promise for future olfactory fMRI studies in the OB and other brain regions that suffer from large susceptibility artifacts.

Differential Changes in Arteriolar Cerebral Blood Volume between Parkinson's Disease Patients with Normal and Impaired Cognition and Mild Cognitive Impairment (MCI) Patients without Movement Disorder - An Exploratory Study.

Cognitive impairment amongst Parkinson's disease (PD) patients is highly prevalent and associated with an increased risk of dementia. There is growing evidence that altered cerebrovascular functions contribute to cognitive impairment. Few studies have compared cerebrovascular changes in PD patients with normal and impaired cognition and those with mild-cognitive-impairment (MCI) without movement disorder. Here, we investigated arteriolar-cerebral-blood-volume (CBVa), an index reflecting the homeostasis of the most actively regulated segment in the microvasculature, using advanced MRI in various brain regions in PD and MCI patients and matched controls. Our goal is to find brain regions with altered CBVa that are specific to PD with normal and impaired cognition, and MCI-without-movement-disorder, respectively. In PD patients with normal cognition (n=10), CBVa was significantly decreased in the substantia nigra, caudate and putamen when compared to controls. In PD patients with impaired cognition (n=6), CBVa showed a decreasing trend in the substantia nigra, caudate and putamen, but was significantly increased in the presupplementary motor area and intracalcarine gyrus compared to controls. In MCI-patients-without-movement-disorder (n=18), CBVa was significantly increased in the caudate, putamen, hippocampus and lingual gyrus compared to controls. These findings provide important information for efforts towards developing biomarkers for the evaluation of potential risk of PD dementia (PDD) in PD patients. The current study is limited in sample size and therefore is exploratory in nature. The data from this pilot study will serve as the basis for power analysis for subsequent studies to further investigate and validate the current findings.

Suture-Button Device Stabilization Following Ring Finger Ray Amputation: A Comparative Cadaver Study.

BACKGROUND: The purpose of this study was to determine whether placing the suture-button device between the long and small finger metacarpals following ring finger ray amputation may better close the intermetacarpal gap and allow early range of motion without increasing the risk of malrotation than soft tissue repair alone. METHODS: We performed ray amputation of the ring finger of 14 cadaver specimens by performing an osteotomy of the base of the ring finger metacarpal and then excising the remainder of the digit. We first performed a soft tissue repair of the transverse metacarpal ligaments and then cycled the fingers in simulated active flexion and extension on a custom computer-controlled device to re-create 6 weeks of range of motion. We then placed a suture-button device across the long and small finger metacarpals and tested the specimens again, thereby using each hand as an internal control. RESULTS: The distance between the ring and small finger metacarpals was reduced following suture-button device placement compared with the initial control; this spacing was maintained following complete cycling of the fingers. The angle between the metacarpals was divergent following soft tissue repair, and then became slightly convergent after insertion of the suture-button device. None of the hands developed clinically relevant scissoring of the digits before or after application of the suture-button device. CONCLUSIONS: The suture-button device provides stable fixation to withstand early range of motion following ring finger ray amputation and significantly closes the gap and angle between the adjacent metacarpals without causing scissoring.

Early Weightbearing After Operatively Treated Ankle Fractures: A Biomechanical Analysis.

BACKGROUND: No consensus exists regarding the timing of weightbearing after surgical fixation of unstable traumatic ankle fractures. We evaluated fracture displacement and timing of displacement with simulated early weightbearing in a cadaveric model. METHODS: Twenty-four fresh-frozen lower extremities were assigned to Group 1, bimalleolar ankle fracture (n=6); Group 2, trimalleolar ankle fracture with unfixed small posterior malleolar fracture (n=9); or Group 3, trimalleolar ankle fracture with fixed large posterior malleolar fracture (n=9) and tested with axial compressive load at 3 Hz from 0 to 1000 N for 250 000 cycles to simulate 5 weeks of full weightbearing. Displacement was measured by differential variable reluctance transducer. RESULTS: The average motion at all fracture sites in all groups was significantly less than 1 mm (P < .05). Group 1 displacement of the lateral and medial malleolus fracture was 0.1±0.1 mm and 0.4±0.4 mm, respectively. Group 2 displacement of the lateral, medial, and posterior malleolar fracture was 0.6±0.4 mm, 0.5±0.4 mm, and 0.5±0.6 mm, respectively. Group 3 displacement of the lateral, medial, and posterior malleolar fracture was 0.1±0.1 mm, 0.5±0.7 mm, and 0.5±0.4 mm, respectively. The majority of displacement (64.0% to 92.3%) occurred in the first 50 000 cycles. There was no correlation between fracture displacement and bone mineral density. CONCLUSION: No significant fracture displacement, no hardware failure, and no new fractures occurred in a cadaveric model of early weightbearing in unstable ankle fracture after open reduction and internal fixation. CLINICAL RELEVANCE: This study supports further investigation of early weightbearing postoperative protocols after fixation of unstable ankle fractures.