Rapid imaging of intravenous gadolinium-based contrast agent (GBCA) entering ventricular cerebrospinal fluid (CSF) through the choroid plexus in healthy human subjects.

BACKGROUND: Pathways for intravenously administered gadolinium-based-contrast-agents (GBCAs) entering cerebrospinal-fluid (CSF) circulation in the human brain are not well-understood. The blood-CSF-barrier (BCSFB) in choroid-plexus (CP) has long been hypothesized to be a main entry-point for intravenous-GBCAs into CSF. Most existing studies on this topic were performed in animals and human patients with various diseases. Results in healthy human subjects are limited. Besides, most studies were performed using MRI methods with limited temporal resolution and significant partial-volume effects from blood and CSF. METHODS: This study employs the recently developed dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI approach to measure GBCA-distribution in the CSF immediately and 4 h after intravenous-GBCA administration in healthy subjects. With a temporal resolution of 10 s, cDSC MRI can track GBCA-induced CSF signal changes during the bolus phase, which has not been investigated previously. It employs a long echo-time (TE = 1347 ms) to suppress tissue and blood signals so that pure CSF signal is detected with minimal partial-volume effects. GBCA concentration in the CSF can be estimated from cDSC MRI. In this study, cDSC and FLAIR MRI were performed immediately and 4 h after intravenous GBCA administration in 25 healthy volunteers (age 48.9 ± 19.5 years; 14 females). Paired t-tests were used to compare pre-GBCA and post-GBCA signal changes, and their correlations with age were evaluated using Pearson-correlation-coefficients. RESULTS: At ~ 20 s post-GBCA, GBCA-induced cDSC signal changes were detected in the CSF around CP (ΔS/S = - 2.40 ± 0.30%; P < .001) but not in the rest of lateral ventricle (LV). At 4 h, significant GBCA-induced cDSC signal changes were observed in the entire LV (ΔS/S = - 7.58 ± 3.90%; P = .002). FLAIR MRI showed a similar trend. GBCA-induced CSF signal changes did not correlate with age. CONCLUSIONS: These results provided direct imaging evidence that GBCAs can pass the BCSFB in the CP and enter ventricular CSF immediately after intravenous administration in healthy human brains. Besides, our results in healthy subjects established a basis for clinical studies in brain diseases exploiting GBCA-enhanced MRI to detect BCSFB dysfunction.

Imaging arterial and venous vessels using Iron Dextran enhanced multi-echo 3D gradient echo MRI at 7T.

Iron Dextran is a widely used iron oxide compound to treat iron-deficiency anemia patients in the clinic. Similar to other iron oxide compounds such as Ferumoxytol, it can also be used off-label as an intravascular magnetic resonance imaging (MRI) contrast agent due to its strong iron-induced T2 and T2* shortening effects. In this study, we seek to evaluate the feasibility of using Iron Dextran enhanced multi-echo susceptibility weighted imaging (SWI) MRI at 7T to image arterial and venous blood vessels in the human brain. Phantom experiments were performed to measure the r2* relaxivity for Iron Dextran in blood, based on which the SWI sequence was optimized. Pre- and post-infusion MR images were acquired in human subjects from which maps of arteries and veins were extracted. The post-contrast SWI images showed enhanced susceptibility difference between blood and the surrounding tissue in both arteries and veins. Our results showed that the proposed Iron Dextran enhanced multi-echo SWI approach allowed the visualization of blood vessels with diameters down to ~100 µm, including small blood vessels supplying and draining small brain structures such as the hippocampus. We conclude that Iron Dextran can be an alternative iron-based MRI contrast agent for blood vessel imaging in the human brain.

Inflammation-related pathology in the olfactory epithelium: its impact on the olfactory system in psychotic disorders.

Smell deficits and neurobiological changes in the olfactory bulb (OB) and olfactory epithelium (OE) have been observed in schizophrenia and related disorders. The OE is the most peripheral olfactory system located outside the cranium, and is connected with the brain via direct neuronal projections to the OB. Nevertheless, it is unknown whether and how a disturbance of the OE affects the OB in schizophrenia and related disorders. Addressing this gap would be the first step in studying the impact of OE pathology in the disease pathophysiology in the brain. In this cross-species study, we observed that chronic, local OE inflammation with a set of upregulated genes in an inducible olfactory inflammation (IOI) mouse model led to a volume reduction, layer structure changes, and alterations of neuron functionality in the OB. Furthermore, IOI model also displayed behavioral deficits relevant to negative symptoms (avolition) in parallel to smell deficits. In first episode psychosis (FEP) patients, we observed a significant alteration in immune/inflammation-related molecular signatures in olfactory neuronal cells (ONCs) enriched from biopsied OE and a significant reduction in the OB volume, compared with those of healthy controls (HC). The increased expression of immune/inflammation-related molecules in ONCs was significantly correlated to the OB volume reduction in FEP patients, but no correlation was found in HCs. Moreover, the increased expression of human orthologues of the IOI genes in ONCs was significantly correlated with the OB volume reduction in FEP, but not in HCs. Together, our study implies a potential mechanism of the OE-OB pathology in patients with psychotic disorders (schizophrenia and related disorders). We hope that this mechanism may have a cross-disease implication, including COVID-19-elicited mental conditions that include smell deficits.

Inflammation-related pathology in the olfactory epithelium: its impact on the olfactory system in psychotic disorders.

Smell deficits and neurobiological changes in the olfactory bulb (OB) and olfactory epithelium (OE) have been observed in schizophrenia and related disorders. The OE is the most peripheral olfactory system located outside the cranium, and is connected with the brain via direct neuronal projections to the OB. Nevertheless, it is unknown whether and how a disturbance of the OE affects the OB in schizophrenia and related disorders. Addressing this gap would be the first step in studying the impact of OE pathology in the disease pathophysiology in the brain. In this cross-species study, we observed that chronic, local OE inflammation with a set of upregulated genes in an inducible olfactory inflammation (IOI) mouse model led to a volume reduction, layer structure changes, and alterations of neuron functionality in the OB. Furthermore, IOI model also displayed behavioral deficits relevant to negative symptoms (avolition) in parallel to smell deficits. In first episode psychosis (FEP) patients, we observed a significant alteration in immune/inflammation-related molecular signatures in olfactory neuronal cells (ONCs) enriched from biopsied OE and a significant reduction in the OB volume, compared with those of healthy controls (HC). The increased expression of immune/inflammation-related molecules in ONCs was significantly correlated to the OB volume reduction in FEP patients, but no correlation was found in HCs. Moreover, the increased expression of human orthologues of the IOI genes in ONCs was significantly correlated with the OB volume reduction in FEP, but not in HCs. Together, our study implies a potential mechanism of the OE-OB pathology in patients with psychotic disorders (schizophrenia and related disorders). We hope that this mechanism may have a cross-disease implication, including COVID-19-elicited mental conditions that include smell deficits.

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.

Acoustic Noise Levels in High-field Magnetic Resonance Imaging Scanners.

7-Tesla (T) magnetic resonance imaging may allow for higher resolution images but may produce greater acoustic noise than 1.5- and 3-T scanners. We sought to characterize the intensity of acoustic noise from 7- versus 3-T scanners. A-weighted sound pressure levels from 5 types of pulse sequences used for brain and inner ear imaging in 3- and 7-T scanners were measured. Time-averaged sound level and maximum sound levels generated for each sequence were compared. Time-averaged sound levels exceeded 95 dB and reached maximums above 105 dB on the majority of 3- and 7-T scans. The mean time-averaged sound level and maximum sound level across pulse sequences were greater in 7- than 3-T (105.6 vs 91.4, P = .01; 114.0 vs. 96.5 dB, P < .01). 7- and 3-T magnetic resonance imaging scanners produce high levels of acoustic noise that exceed acceptable safety limits, emphasizing the need for active and passive noise protection.

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.

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.

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.

Robust RF shimming and small-tip-angle multispoke pulse design with finite-difference regularization.

PURPOSE: A new regularizer is proposed for the magnitude least-squares optimization algorithm, to ensure robust parallel transmit RF shimming and small-tip-angle multispoke pulse designs for ultrahigh-field MRI. METHODS: A finite-difference regularization term is activated as an additional regularizer in the iterative magnitude-least-squares based pulse design algorithm when an unwanted flip angle null distribution is detected. Both simulated and experimental B1+ maps from different transmit arrays and different human subjects at 7 T were used to evaluate the proposed algorithm. The algorithm was further demonstrated in experiment with dynamic multislice RF shimming for a single-shot gradient-echo EPI for human functional MRI at 7 T. RESULTS: The proposed finite-difference regularizer effectively prevented excitation null to be formed for RF shimming and small-tip-angle multispoke pulses, and improved the latter with a monotonic trade-off relationship between flip angle error and RF power. The proposed algorithm was demonstrated to be effective with several head-array geometries by simulation and with a commercial head array with 12 healthy human subjects by experiment. During a functional MRI scan at 7 T with dynamic RF shimming, the proposed algorithm ensured high image SNR throughout the human brain, compared with near-complete local signal loss by the conventional magnitude-least-squares algorithm. CONCLUSION: Using finite-difference regularization to avoid unwanted solutions, the robustness of RF shimming and small-tip-angle multispoke pulse design algorithms are improved, with better flip angle homogeneity and a monotonic trade-off relationship between flip angle error and RF power.

Impaired response of cerebral oxygen metabolism to visual stimulation in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disease caused by a CAG triplet repeat expansion in the Huntingtin gene. Metabolic and microvascular abnormalities in the brain may contribute to early physiological changes that subserve the functional impairments in HD. This study is intended to investigate potential abnormality in dynamic changes in cerebral blood volume (CBV) and cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2) in the brain in response to functional stimulation in premanifest and early manifest HD patients. A recently developed 3-D-TRiple-acquisition-after-Inversion-Preparation magnetic resonance imaging (MRI) approach was used to measure dynamic responses in CBV, CBF, and CMRO2 during visual stimulation in one single MRI scan. Experiments were conducted in 23 HD patients and 16 healthy controls. Decreased occipital cortex CMRO2 responses were observed in premanifest and early manifest HD patients compared to controls (P < 0.001), correlating with the CAG-Age Product scores in these patients (R2 = 0.4, P = 0.001). The results suggest the potential value of this reduced CMRO2 response during visual stimulation as a biomarker for HD and may illuminate the role of metabolic alterations in the pathophysiology of HD.

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.

Fast whole brain MR imaging of dynamic susceptibility contrast changes in the cerebrospinal fluid (cDSC MRI).

PURPOSE: The circulation of cerebrospinal fluid (CSF) is closely associated with many aspects of brain physiology. When gadolinium(Gd)-based contrast is administered intravenously, pre- and post-contrast MR signal changes can often be observed in the CSF at certain locations within the intra-cranial space, mainly due to the lack of a blood-brain barrier in the dural blood vessels. This study aims to develop and systemically optimize MRI sequences that can detect dynamic signal changes in the CSF after Gd administration with a sub-millimeter spatial resolution, a temporal resolution of <10 s, and whole brain coverage. METHODS: Bloch simulations were performed to determine optimal imaging parameters for maximum CSF contrast before and after Gd injection. Simulations were validated with phantom scans. An optimized turbo-spin-echo (TSE) sequence was performed on healthy volunteers on 3T and 7T. RESULTS: Simulation results agreed well with phantom scans. In human scans, dynamic signal changes after Gd injection in the CSF were detected at several locations where cerebral lymphatic vessels were identified in previous studies. The concentration of Gd in CSF in these regions was estimated to be approximately 0.2 mmol/L. CONCLUSION: Dynamic signal changes induced by the distribution of Gd in the CSF can be detected in healthy human subjects with an optimized TSE sequence. The proposed methodology does not rely on any particular theory on CSF circulation. We expect it to be useful for studies on CSF circulation and cerebral lymphatic vessels in the brain.

Altered functional connectivity between sub-regions in the thalamus and cortex in schizophrenia patients measured by resting state BOLD fMRI at 7T.

The thalamus is a small brain structure that relays neuronal signals between subcortical and cortical regions. Abnormal thalamocortical connectivity in schizophrenia has been reported in previous studies using blood-oxygenation-level-dependent (BOLD) functional MRI (fMRI) performed at 3T. However, anatomically the thalamus is not a single entity, but is subdivided into multiple distinct nuclei with different connections to various cortical regions. We sought to determine the potential benefit of using the enhanced sensitivity of BOLD fMRI at ultra-high magnetic field (7T) in exploring thalamo-cortical connectivity in schizophrenia based on subregions in the thalamus. Seeds placed in thalamic subregions of 14 patients and 14 matched controls were used to calculate whole-brain functional connectivity. Our results demonstrate impaired thalamic connectivity to the prefrontal cortex and the cerebellum, but enhanced thalamic connectivity to the motor/sensory cortex in schizophrenia. This altered functional connectivity significantly correlated with disease duration in the patients. Remarkably, comparable effect sizes observed in previous 3T studies were detected in the current 7T study with a heterogeneous and much smaller cohort, providing evidence that ultra-high field fMRI may be a powerful tool for measuring functional connectivity abnormalities in schizophrenia. Further investigation with a larger cohort is merited to validate the current findings.

Distal fibular malrotation and lateral ankle contact characteristics.

BACKGROUND: Any amount of malreduction of the syndesmotic joint compared with the uninjured syndesmosis has been associated with an adverse effect on functional outcome. The amount of malrotation that may lead to clinically relevant pressure change in this joint has not been reported. Our purpose was to determine whether small degrees of external and internal malrotation would be associated with statistically significant changes in contact pressure in the tibiofibular and talofibular articulations. METHODS: Twelve cadaveric ankles were osteotomized above the syndesmosis and instrumented with a rotatable distal fibula plate. Sensors at the distal tibiofibular and talofibular articulations recorded contact pressure and area at neutral position and at 5 and 10° of external and internal malrotation through a full range of ankle motion. RESULTS: Compared with neutral rotation, there was a significant decrease in contact pressure at the talofibular articulation with external rotation of 5° (103±113kPa versus 52±69kPa; P=0.01) and 10° (43±62kPa; P=0.01) in plantarflexion.Contact pressure at the tibiofibular articulation in plantarflexion increased with 10° of internal malrotation compared with neutral rotation (56±30kPa versus 74±38kPa; P=0.05) in plantarflexion. Contact area decreased significantly with plantarflexion and 10° of external rotation and increased significantly in plantarflexion and after cyclic loading with 10° of internal rotation (P≤0.05). CONCLUSION: Any degree of distal fibular external rotation significantly reduced contact pressure in the talofibular articulation with plantarflexion. A minimal increase in contact pressure was found in the tibiofibular and talofibular joints with plantarflexion and mild internal rotation of 5°, but pressure increased significantly in both articulations with 10° of internal rotation. The findings support clinical findings that subtle degrees of fibular malrotation may be associated with alteration of lateral ankle mechanics. LEVEL OF EVIDENCE: Controlled biomechanical study.

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.

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.