Background: The anterior cruciate ligament (ACL) is loaded under tension when the tibia translates anteriorly relative to the femur. The shape of the articular surfaces of the tibiofemoral joint may influence the amount of anterior tibial translation under compressive loading. Thus, a steep lateral tibial plateau and a shallow medial plateau are thought to be risk factors for ACL injury. Purpose/Hypothesis: The purpose of this study was to evaluate whether tibial plateau slope and depth influence peak ACL strain during a single-leg jump. We hypothesized that there would be a significant correlation between tibial plateau slope and depth with ACL strain. Study Design: Descriptive laboratory study. Methods: A total of 17 healthy participants (8 male, 9 female) were assessed using magnetic resonance imaging (MRI) and high-speed biplanar radiography to obtain peak ACL strain during a single-leg jump. Two orthopaedic surgeons used the sagittal plane MRI scans to measure the medial and lateral tibial plateau slopes and the medial tibial plateau depth. The intraclass correlation coefficient was used to assess measurement reliability, and the Spearman rank correlation was used to evaluate the relationship between measurements of tibial morphology and peak ACL strain during the single-leg jump. Results: The overall range of intraclass correlation coefficients for intra- and interrater reliability of the medial and lateral tibial plateau slopes and medial plateau depth was 0.59 to 0.97. No significant correlations were found between peak ACL strain and any of the slope or depth measurements. Conclusion: In this cohort of healthy participants, correlations between any of the tibial plateau measurements with peak ACL strain during a single-leg jump were not detected. These findings are consistent with prior work, suggesting that tibial plateau slope and depth may not be linked to risk for ACL rupture. However, it is possible that tibial plateau morphology may interact with other factors to increase ACL injury risk or that individuals with extreme slope angles may produce differing results. Clinical Relevance: This study enhances the knowledge of the loading mechanisms for the ACL and thus improves the understanding of risk factors for ACL injury.

Objective: To assess the in vivo relationship between the mechanical response of intervertebral discs (IVDs) to dynamic activity and IVD biochemical composition assessed via T1rho relaxation imaging.Design: Eighteen asymptomatic participants with no history of low back pain (LBP), injury, or surgery underwent magnetic resonance (MR) imaging of their lumbar spine prior to and immediately following a treadmill walking "stress test." Anatomic (SPACE, FLASH) MR images were obtained pre-and post -ex-ercise and utilized to measure IVD mechanical deformation. Quantitative (T1rho) imaging was performed pre-exercise to reflect IVD composition. Pre-exercise anatomic images were also utilized to assess IVD degenerative status based on the modified Pfirrmann scale. To quantify mechanical response, 3D surface models of the L1-L2-L5-S1 IVDs were created from manual segmentations of pre-and post-exercise anatomic images and utilized to assess changes in IVD height. IVD strain (%) was defined as change in IVD height normalized to pre-activity height. Linear mixed models were used to assess the relationships between IVD mechanical deformation (strain), composition (T1rho relaxation time), and degenerative status (Pfirrmann grade).Results: Increased compressive IVD strain was associated with lower T1rho relaxation times in the nu-cleus pulposus (NP) of the disc (bT1rho = 5.07, CI : [1.52, 7.77[, R2marg = 0.52, p = 0.005). Thus, an inverse relationship between IVD strain and NP T1rho relaxation time was observed. Conclusion: The in vivo mechanical response of the IVD to the "stress test" was sensitive to differences in NP composition. The results of this study suggest that quantification of in vivo IVD mechanical function and composition may provide insight into IVD health.(c) 2022 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Background: Noncontact anterior cruciate ligament (ACL) injuries typically occur during deceleration movements such as landing or cutting. However, conflicting data have left the kinematic mechanisms leading to these injuries unclear. Quantifying the influence of sagittal and coronal plane knee kinematics on in vivo ACL strain may help to elucidate noncontact ACL injury mechanisms. Purpose/Hypothesis: The purpose of this study was to measure in vivo sagittal and coronal plane knee kinematics and ACL strain during a single-leg jump. We hypothesized that ACL strain would be modulated primarily by motion in the sagittal plane and that limited coronal plane motion would be measured during this activity. Study Design: Descriptive laboratory study. Methods: Seventeen healthy participants (8 male/9 female) underwent magnetic resonance imaging (MRI) followed by high-speed biplanar radiography, obtained as participants performed a single-leg jump. Three-dimensional models of the femur, tibia, and associated ACL attachment site footprints were created from the MRIs and registered to the radiographs to reproduce the position of the knee during the jump. ACL strain, knee flexion/extension angles, and varus/valgus angles were measured throughout the jump. Spearman rank correlations were used to assess relationships between mean ACL strain and kinematic variables. Results: Mean ACL strain increased with decreasing knee flexion angle (ρ = −0.3; P = .002), and local maxima in ACL strain occurred with the knee in a straight position in both the sagittal and the coronal planes. In addition, limited coronal plane motion (varus/valgus angle) was measured during this activity (mean ± SD, −0.5°± 0.3°). Furthermore, we did not detect a statistically significant relationship between ACL strain and varus/valgus angle (ρ = −0.01; P = .9). Conclusion: ACL strain was maximized when the knee was in a straight position in both the sagittal and coronal planes. Participants remained in <1° of varus/valgus position on average throughout the jump. As a ligament under elevated strain is more vulnerable to injury, landing on a straight knee may be an important risk factor for ACL rupture. Clinical Relevance: These data may improve understanding of risk factors for noncontact ACL injury, which may be useful in designing ACL injury prevention programs.

Background: Quadriceps loading of the anterior cruciate ligament (ACL) may play a role in the noncontact mechanism of ACL injury. Musculoskeletal modeling techniques are used to estimate the intrinsic force of the quadriceps acting at the knee joint. Purpose/Hypothesis: The purpose of this paper was to develop a novel musculoskeletal model of in vivo quadriceps force during dynamic activity. We used the model to estimate quadriceps force in relation to ACL strain during a single-leg jump. We hypothesized that quadriceps loading of the ACL would reach a local maximum before initial ground contact with the knee positioned in extension. Study Design: Descriptive laboratory study. Methods: Six male participants underwent magnetic resonance imaging in addition to high-speed biplanar radiography during a single-leg jump. Three-dimensional models of the knee joint, including the femur, tibia, patellofemoral cartilage surfaces, and attachment-site footprints of the patellar tendon, quadriceps tendon, and ACL, were created from the magnetic resonance imaging scans. The bone models were registered to the biplanar radiographs, thereby reproducing the positions of the knee joint at the time of radiographic imaging. The magnitude of quadriceps force was determined for each knee position based on a 3-dimensional balance of the forces and moments of the patellar tendon and the patellofemoral cartilage contact acting on the patella. Knee kinematics and ACL strain were determined for each knee position. Results: A local maximum in average quadriceps force of approximately 6500 N (8.4× body weight) occurred before initial ground contact. ACL strain increased concurrently with quadriceps force when the knee was positioned in extension. Conclusion: This novel participant-specific modeling technique provides estimates of in vivo quadriceps force during physiologic dynamic loading. A local maximum in quadriceps force before initial ground contact may tension the ACL when the knee is positioned in extension. Clinical Relevance: These data contribute to understanding noncontact ACL injury mechanisms and the potential role of quadriceps activation in these injuries.

Some cadaveric studies have indicated that the anterior cruciate ligament (ACL) consists of anteromedial (AM) and posterolateral (PL) bundles that function reciprocally with motion. However, several in vivo imaging studies have indicated that ACL subdivisions elongate during knee extension. Whether the ACL is a single structure or consists of different bundles with distinct function is debated. We hypothesized that both the AM and PL ACL subdivisions would undergo relative elongation with knee extension during gait.

High body mass index (BMI) and obesity have been implicated as risk factors for lumbar degenerative disc disease and low back pain. Despite this, there is limited in vivo data to quantify how obesity influences the mechanical function of intervertebral discs (IVD) in response to activities of daily living. Recently, our lab has developed methodologies to non-invasively measure in vivo IVD deformation resulting from activities of daily living using magnetic resonance (MR) imaging and solid modeling techniques. This pilot study expands on these methodologies to assess how BMI influences IVD deformation following treadmill walking in eight asymptomatic individuals. Ordinary least squares regression analyses revealed a statistically significant relationship between BMI and compressive deformation (strain (%)) in the L5-S1 IVD (R2 = 0.61, p < 0.05). This relationship was weaker in the L3-L4 (R2 = 0.28, p > 0.05) and L4-L5 IVDs (R2 = 0.28, p > 0.05). Importantly, no relationship between pre-exercise disc height and BMI was identified (p > 0.05). Therefore, the results of this study suggest that BMI may alter the mechanical response of lumbar spine IVDs, particularly at the L5-S1 level. Furthermore, the observed relationship between increased BMI and IVD compressive deformation, in the absence of a detected relationship between pre-exercise disc height and BMI, suggests that changes in IVD mechanical function may be more sensitive to alterations in disc health than static clinical imaging alone. This finding highlights the importance of quantifying disc mechanical function when examining the relationship between BMI and IVD degeneration.

Background: There is little in vivo data that describe the relationships between patellar tendon orientation, patellar tendon strain, and anterior cruciate ligament (ACL) strain during dynamic activities. Quantifying how the quadriceps load the ACL via the patellar tendon is important for understanding ACL injury mechanisms. Hypothesis: We hypothesized that flexion angle, patellar tendon orientation, and patellar tendon strain influence ACL strain during a single-leg jump. Specifically, we hypothesized that patellar tendon and ACL strains would increase concurrently when the knee is positioned near extension during the jump. Study Design: Descriptive laboratory study. Methods: Models of the femur, tibia, ACL, patellar tendon, and quadriceps tendon attachment sites of 8 male participants were generated from magnetic resonance imaging (MRI). High-speed biplanar radiographs during a single-leg jump were obtained. The bone models were registered to the radiographs, thereby reproducing the in vivo positions of the bones, ligament, and tendon attachment sites. Flexion angle, patellar tendon orientation, patellar tendon strain, and ACL strain were measured from the registered models. ACL and patellar tendon strains were approximated by normalizing their length at each knee position to their length at the time of MRI. Two separate bivariate linear regression models were used to assess relationships between flexion angle and patellar tendon orientation and between ACL strain and patellar tendon strain. A multivariate linear regression model was used to assess whether flexion angle and patellar tendon strain were significant predictors of ACL strain during the inflight and landing portions of the jump. Results: Both flexion angle and patellar tendon strain were significant predictors (P < .05) of ACL strain. These results indicate that elevated ACL and patellar tendon strains were observed concurrently when the knee was positioned near extension. Conclusion: Concurrent increases in patellar tendon and ACL strains indicate that the quadriceps load the ACL via the patellar tendon when the knee is positioned near extension. Clinical Relevance: Increased ACL strain when the knee is positioned near extension before landing may be due to quadriceps contraction. Thus, landing with unanticipated timing on an extended knee may increase vulnerability to ACL injury as a taut ligament is more likely to fail.

The purpose of this study was to measure in vivo attachment site to attachment site lengths and strains of the anterior cruciate ligament (ACL) and its bundles throughout a full cycle of treadmill gait. To obtain these measurements, models of the femur, tibia, and associated ACL attachment sites were created from magnetic resonance (MR) images in 10 healthy subjects. ACL attachment sites were subdivided into anteromedial (AM) and posterolateral (PL) bundles. High-speed biplanar radiographs were obtained as subjects ambulated at 1 m/s. The bone models were registered to the radiographs, thereby reproducing the in vivo positions of the bones and ACL attachment sites throughout gait. The lengths of the ACL and both bundles were estimated as straight line distances between attachment sites for each knee position. Increased attachment to attachment ACL length and strain were observed during midstance (length = 28.5 ± 2.6 mm, strain = 5 ± 4%, mean ± standard deviation), and heel strike (length = 30.5 ± 3.0 mm, strain = 12 ± 5%) when the knee was positioned at low flexion angles. Significant inverse correlations were observed between mean attachment to attachment ACL lengths and flexion (rho = -0.87, p < 0.001), as well as both bundle lengths and flexion (rho = -0.86, p < 0.001 and rho = -0.82, p < 0.001, respectively). AM and PL bundle attachment to attachment lengths were highly correlated throughout treadmill gait (rho = 0.90, p < 0.001). These data can provide valuable information to inform design criteria for ACL grafts used in reconstructive surgery, and may be useful in the design of rehabilitation and injury prevention protocols.

BACKGROUND:Some cadaveric studies have indicated that the anterior cruciate ligament (ACL) consists of anteromedial and posterolateral bundles that display reciprocal function with regard to knee flexion. However, several in vivo imaging studies have suggested that these bundles elongate in parallel with regard to flexion. Furthermore, the most appropriate description of the functional anatomy of the ACL is still debated, with the ACL being described as consisting of 2 or 3 bundles or as a continuum of fibers.HYPOTHESIS:As long as their origination and termination locations are defined within the ACL attachment site footprints, ACL bundles elongate in parallel with knee extension during gait.STUDY DESIGN:Descriptive laboratory study.METHODS:High-speed biplanar radiographs of the right knee joint were obtained during gait in 6 healthy male participants (mean ± SD: body mass index, 25.5 ± 1.2 kg/m2; age, 29.2 ± 3.8 years) with no history of lower extremity injury or surgery. Three-dimensional models of the right femur, tibia, and ACL attachment sites were created from magnetic resonance images. The bone models were registered to the biplanar radiographs, thereby reproducing the in vivo positions of the knee joint. For each knee position, the distances between the centroids of the ACL attachment sites were used to represent ACL length. The lengths of 1000 virtual bundles were measured for each participant by randomly sampling locations on the attachment site surfaces and measuring the distances between each pair of locations. Spearman rho rank correlations were performed between the virtual bundle lengths and ACL length.RESULTS:The virtual bundle lengths were highly correlated with the length of the ACL, defined as the distance between the centroids of the attachment sites (rho = 0.91 ± 0.1, across participants; P < 5 × 10-5). The lengths of the bundles that originated and terminated in the anterior and medial aspects of the ACL were positively correlated (rho = 0.81 ± 0.1; P < 5 × 10-5) with the lengths of the bundles that originated and terminated in the posterior and lateral aspects of the ACL.CONCLUSION:As long as their origination and termination points are specified within the footprint of the attachment sites, ACL bundles elongate in parallel as the knee is extended.CLINICAL RELEVANCE:These data elucidate ACL functional anatomy and may help guide ACL reconstruction techniques.

Background: The in vivo mechanics of the anterior cruciate ligament (ACL) and its bundles during dynamic activities are not completely understood. An improved understanding of how the ACL stabilizes the knee is likely to aid in the identification and prevention of injurious maneuvers. Purpose/Hypothesis: The purpose was to measure in vivo ACL strain during a single-legged jump through use of magnetic resonance imaging (MRI) and high-speed biplanar radiography. We hypothesized that ACL strain would increase with the knee near extension, and a peak in ACL strain would occur just before landing from the jump, potentially due to quadriceps contraction in anticipation of landing. Study Design: Descriptive laboratory study. Methods: Models of the femur, tibia, and ACL attachment sites of 8 male participants were generated from MRI scans through use of solid modeling. High-speed biplanar radiographs were obtained from these participants as they performed a single-legged jump. The bone models were registered to the biplanar radiographs, thereby reproducing the in vivo positions of the joint throughout the jump. ACL and bundle elongations were defined as the centroid to centroid distances between attachment sites for each knee position. ACL strain was defined as ACL length normalized to its length measured in the position of the knee at the time of MRI. Results: Peaks in ACL strain were observed before toe-off and 55 ± 35 milliseconds before initial ground contact. These peaks were associated with the knee positioned at low flexion angles. Mean ACL strain was inversely related to mean flexion angle (rho = −0.73, P < .001), such that ACL strain generally increased with knee extension throughout the jumping motion. ACL bundle lengths were significantly (rho > 0.85, P < .001) correlated with overall ACL length. Conclusion: These findings provide insight into how landing in extension can increase the risk of ACL injury. Specifically, this study shows that peak ACL strain can occur just before landing from a single-legged jump. Thus, when an individual lands on an extended knee, the ACL is relatively taut, which may make it particularly vulnerable to injury, especially in the presence of a movement perturbation or unanticipated change in landing strategy. Clinical Relevance: This study provides a novel measurement of dynamic ACL strain during an athletic maneuver and lends insight into how landing in extension can increase the likelihood of ACL failure.

A potential cause of non-contact anterior cruciate ligament (ACL) injury is landing on an extended knee. In line with this hypothesis, studies have shown that the ACL is elongated with decreasing knee flexion angle. Furthermore, at low flexion angles the patellar tendon is oriented to increase the anterior shear component of force acting on the tibia. This indicates that knee extension represents a position in which the ACL is taut, and thus may have an increased propensity for injury, particularly in the presence of excessive force acting via the patellar tendon. However, there is very little in vivo data to describe how patellar tendon orientation and ACL elongation interact during flexion. Therefore, this study measured the patellar tendon tibial shaft angle (indicative of the relative magnitude of the shear component of force acting via the patellar tendon) and ACL length in vivo as subjects performed a quasi-static lunge at varying knee flexion angles. Spearman rho rank correlations within each individual revealed that flexion angles were inversely correlated to both ACL length (rho = -0.94 +/- 0.07, mean +/- standard deviation, p < 0.05) and patellar tendon tibial shaft angle (rho = -0.99 +/- 0.01, p < 0.05). These findings indicate that when the knee is extended, the ACL is both elongated and the patellar tendon tibial shaft angle is increased, resulting in a relative increase in anterior shear force on the tibia acting via the patellar tendon. Therefore, these data support the hypothesis that landing with the knee in extension is a high risk scenario for ACL injury. (C) 2019 Elsevier Ltd. All rights reserved.

Osteoarthritis (OA) is the most common joint disease in the world, with an age-associated increase in both incidence and prevalence. Clinical and epidemiologic research is crucial to better understand risk factors for disease, find the best treatments for symptoms, and identify therapies to slow down or even prevent disease progression. This paper is based on a systematic review of the osteoarthritis literature published in English between 2017/05/01 and 2018/04/25, with a focus on papers which have the potential to improve patient care, or which suggest novel areas for future research.

Background: Knee positions involved in noncontact anterior cruciate ligament (ACL) injury have been studied via analysis of injury videos. Positions of high ACL strain have been identified in vivo. These methods have supported different hypotheses regarding the role of knee abduction in ACL injury. Purpose/Hypothesis: The purpose of this study was to compare knee abduction angles measured by 2 methods: using a 3-dimensional (3D) coordinate system based on anatomic features of the bones versus simulated 2-dimensional (2D) videographic analysis. We hypothesized that knee abduction angles measured in a 2D videographic analysis would differ from those measured from 3D bone anatomic features and that videographic knee abduction angles would depend on flexion angle and on the position of the camera relative to the patient. Study Design: Descriptive laboratory study. Methods: Models of the femur and tibia were created from magnetic resonance images of 8 healthy male participants. The models were positioned to match biplanar fluoroscopic images obtained as participants posed in lunges of varying flexion angles (FLAs). Knee abduction angle was calculated from the positioned models in 2 ways: (1) varus-valgus angle (VVA), defined as the angle between the long axis of the tibia and the femoral transepicondylar axis by use of a 3D anatomic coordinate system; and (2) coronal plane angle (CPA), defined as the angle between the long axis of the tibia and the long axis of the femur projected onto the tibial coronal plane to simulate a 2D videographic analysis. We then simulated how changing the position of the camera relative to the participant would affect knee abduction angles. Results: During flexion, when CPA was calculated from a purely anterior or posterior view of the joint—an ideal scenario for measuring knee abduction from 2D videographic analysis—CPA was significantly different from VVA (P < .0001). CPA also varied substantially with the position of the camera relative to the participant. Conclusion: How closely CPA (derived from 2D videographic analysis) relates to VVA (derived from a 3D anatomic coordinate system) depends on FLA and camera orientation. Clinical Relevance: This study provides a novel comparison of knee abduction angles measured from 2D videographic analysis and those measured within a 3D anatomic coordinate system. Consideration of these findings is important when interpreting 2D videographic data regarding knee abduction angle in ACL injury.

BACKGROUND:Changes in knee kinematics after anterior cruciate ligament (ACL) injury may alter loading of the cartilage and thus affect its homeostasis, potentially leading to the development of posttraumatic osteoarthritis. However, there are limited in vivo data to characterize local changes in cartilage thickness and strain in response to dynamic activity among patients with ACL deficiency. PURPOSE/HYPOTHESIS:The purpose was to compare in vivo tibiofemoral cartilage thickness and cartilage strain resulting from dynamic activity between ACL-deficient and intact contralateral knees. It was hypothesized that ACL-deficient knees would show localized reductions in cartilage thickness and elevated cartilage strains. STUDY DESIGN:Controlled laboratory study. METHODS:Magnetic resonance images were obtained before and after single-legged hopping on injured and uninjured knees among 8 patients with unilateral ACL rupture. Three-dimensional models of the bones and articular surfaces were created from the pre- and postactivity scans. The pre- and postactivity models were registered to each other, and cartilage strain (defined as the normalized difference in cartilage thickness pre- and postactivity) was calculated in regions across the tibial plateau, femoral condyles, and femoral cartilage adjacent to the medial intercondylar notch. These measurements were compared between ACL-deficient and intact knees. Differences in cartilage thickness and strain between knees were tested with multiple analysis of variance models with alpha set at P < .05. RESULTS:Compressive strain in the intercondylar notch was elevated in the ACL-deficient knee relative to the uninjured knee. Furthermore, cartilage in the intercondylar notch and adjacent medial tibia was significantly thinner before activity in the ACL-deficient knee versus the intact knee. In these 2 regions, thinning was significantly influenced by time since injury, with patients with more chronic ACL deficiency (>1 year since injury) experiencing greater thinning. CONCLUSION:Among patients with ACL deficiency, the medial femoral condyle adjacent to the intercondylar notch in the ACL-deficient knee exhibited elevated cartilage strain and loss of cartilage thickness, particularly with longer time from injury. It is hypothesized that these changes may be related to posttraumatic osteoarthritis development. CLINICAL RELEVANCE:This study suggests that altered mechanical loading is related to localized cartilage thinning after ACL injury.

Understanding in vivo joint mechanics during dynamic activity is crucial for revealing mechanisms of injury and disease development. To this end, laboratories have utilized computed tomography (CT) to create 3-dimensional (3D) models of bone, which are then registered to high-speed biplanar radiographic data captured during movement in order to measure in vivo joint kinematics. In the present study, we describe a system for measuring dynamic joint mechanics using 3D surface models of the joint created from magnetic resonance imaging (MRI) registered to high-speed biplanar radiographs using a novel automatic registration algorithm. The use of MRI allows for modeling of both bony and soft tissue structures. Specifically, the attachment site footprints of the anterior cruciate ligament (ACL) on the femur and tibia can be modeled, allowing for measurement of dynamic ACL deformation. In the present study, we demonstrate the precision of this system by tracking the motion of a cadaveric porcine knee joint. We then utilize this system to quantify in vivo ACL deformation during gait in four healthy volunteers.

Anterior cruciate ligament (ACL) deficient patients have an increased rate of patellofemoral joint (PFJ) osteoarthritis (OA) as compared to the general population. Although the cause of post-injury OA is multi-factorial, alterations in joint biomechanics may predispose patients to cartilage degeneration. This study aimed to compare in vivo PFJ morphology and mechanics between ACL deficient and intact knees in subjects with unilateral ACL ruptures. Eight male subjects underwent baseline MRI scans of both knees. They then performed a series of 60 single-legged hops, followed by a post-exercise MRI scan. This process was repeated for the contralateral knee. The MR images were converted into three-dimensional surface models of cartilage and bone in order to assess cartilage thickness distributions and strain following exercise. Prior to exercise, patellar cartilage was significantly thicker in intact knees as compared to ACL deficient knees by 1.8%. In response to exercise, we observed average patellar cartilage strains of 5.4 ± 1.1% and 2.5 ± 1.4% in the ACL deficient and intact knees, respectively. Importantly, the magnitude of patellar cartilage strain in the ACL deficient knees was significantly higher than in the intact knees. However, while trochlear cartilage experienced a mean strain of 2.4 ± 1.6%, there was no difference in trochlear cartilage strain between the ACL deficient and uninjured knees. In summary, we found that ACL deficiency was associated with decreased patellar cartilage thickness and increased exercise-induced patellar cartilage strain when compared to the uninjured contralateral knees.

Impairments in executive function, such as working memory, are almost universal in children with chromosome 22q11.2 deletion syndrome. Delineating the neural underpinnings of these functions would enhance understanding of these impairments. In this study, children and adolescents with 22q11 deletion syndrome were compared with healthy control participants in a functional magnetic resonance imaging (MRI) study of working memory. When the 2-back condition was contrasted with the 1-back and 0-back conditions, the participants with 22q11 deletion syndrome showed lower activation in several brain areas involved in working memory—notably dorsolateral prefrontal cortex, anterior cingulate, and precuneus. This hypoactivation may be due to reduced gray matter volumes or white matter connectivity in the frontal and parietal regions, differences that have previously been documented in children with 22q11 deletion syndrome. Understanding differences in brain function will provide a foundation for future interventions to address the wide range of neurodevelopmental deficits observed in 22q11 deletion syndrome.

Cerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.

Neuropathic pain (NP) is caused by damage to the nervous system, resulting in dysfunction and aberrant pain. The cellular functions (e.g., peripheral neuron spinal cord innervation, neuronal excitability) associated with NP often develop over time and are likely associated with gene expression changes. Gene expression studies on the cells involved in NP (e.g., sensory dorsal root ganglion neurons) are publically available; the mining of these studies may enable the identification of novel targets and the subsequent development of therapies that are essential for improving quality of life for the millions of individuals suffering with NP. Here we analyzed a publically available microarray dataset (GSE30165) in order to identify new RNAs (e.g., messenger RNA (mRNA) isoforms and non-coding RNAs) underlying NP. GSE30165 profiled gene expression in dorsal root ganglion neurons (DRG) and in sciatic nerve (SN) after resection, a NP model. Gene ontological analysis shows enrichment for sensory and neuronal processes. Protein network analysis demonstrates DRG upregulated genes typical to an injury and NP response. Of the top changing genes, 34 and 36% are associated with more than one protein coding isoform in the DRG and SN, respectively. The majority of genes are receptor and enzymes. We identified 15 long non-coding RNAs (lncRNAs) targeting these genes in LNCipedia.org, an online comprehensive lncRNA database. These RNAs represent new therapeutic targets for preventing NP development and this approach demonstrates the feasibility of data reanalysis for their identification.