Joseph C. Giaconi

Morbidity of Direct MR Arthrography

OBJECTIVE The purpose of this study was to determine the incidence and severity of arthrographic pain after intraarticular injection of a gadolinium mixture diluted in normal saline for direct MR arthrography. SUBJECTS AND METHODS From March 2009 until January 2010, 155 consecutive patients underwent direct MR arthrography; 20 patients were lost to follow-up. Patients were contacted by telephone between 3 and 7 days after joint injection. Using an 11-point numeric pain rating scale, patients were asked to report if they had experienced joint pain that was different or more intense than their preinjection baseline, the severity of pain, the duration of pain, time to onset of pain, and eventual resolution of pain. RESULTS The incidence of postarthrographic pain was 66% (89/135), with an average intensity of pain of 4.8 ± 2.4 (range, 1-10). Postarthrographic pain lasted an average of 44.4 ± 30.5 hours (range, 6-168 hours). The time to onset of pain after joint injection was on average 16.6 ± 13.1 hours (range, 4-72 hours). There was no significant difference regarding the severity or incidence of postarthrographic pain between groups on the basis of patient age (p = 0.20 and 0.26), patient sex (p = 0.20 and 0.86), contrast mixture contents (p = 0.83 and 0.49), or joint injected (p = 0.51 and 0.47). No patients experienced any other serious side effects. CONCLUSION Sixty-six percent of patients who undergo direct MR arthrography will experience a fairly severe delayed onset of pain that completely resolves over the course of several days.

Anterior cruciate ligament graft reconstruction: clinical, technical, and imaging overview.

The anterior cruciate ligament (ACL) is one of the most frequently torn ligaments of the knee. With more than 100,000 ACL reconstructions performed yearly in the United States, evaluation of ACL grafts with magnetic resonance imaging is a common occurrence in daily clinical practice. Anterior cruciate ligament reconstructions vary from single bundle, double bundle, selective bundle, and physeal-sparing techniques. Complications of ACL graft reconstructions include graft tears, graft laxity, arthrofibrosis, and hardware failure or migration. This article offers a comprehensive review of ACL reconstruction for the consulting radiologist.

In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs.

Microbubble-enhanced, ultrasound-mediated BMP-6 gene delivery to endogenous progenitor cells induces rapid and efficient repair of critical-sized, nonunion bone fractures in mini-pigs. Bubbles and BMP-6 for bone repair Treatments for bone nonunions (fractures that fail to heal) include surgery and bone grafting. As an alternative to viral gene delivery, Bez et al. developed a two-step therapy. First, endogenous mesenchymal stem/progenitor cells were recruited to the bone nonunion by implanting a collagen sponge in the defect site. Two weeks later, bone morphogenetic protein-6 (BMP-6) plasmid DNA and microbubbles were injected into nonunions, and ultrasound was applied to oscillate the microbubbles, which helped the recruited progenitors take up the BMP-6. This therapy led to transient BMP-6 secretion, bone regeneration, and fracture healing over 6 weeks in critical-sized tibial nonunions in mini-pigs. More than 2 million bone-grafting procedures are performed each year using autografts or allografts. However, both options carry disadvantages, and there remains a clear medical need for the development of new therapies for massive bone loss and fracture nonunions. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would induce efficient bone regeneration and fracture repair. To test this hypothesis, we surgically created a critical-sized bone fracture in the tibiae of Yucatán mini-pigs, a clinically relevant large animal model. A collagen scaffold was implanted in the fracture to facilitate recruitment of endogenous mesenchymal stem/progenitor cells (MSCs) into the fracture site. Two weeks later, transcutaneous ultrasound-mediated reporter gene delivery successfully transfected 40% of cells at the fracture site, and flow cytometry showed that 80% of the transfected cells expressed MSC markers. Human bone morphogenetic protein-6 (BMP-6) plasmid DNA was delivered using ultrasound in the same animal model, leading to transient expression and secretion of BMP-6 localized to the fracture area. Micro–computed tomography and biomechanical analyses showed that ultrasound-mediated BMP-6 gene delivery led to complete radiographic and functional fracture healing in all animals 6 weeks after treatment, whereas nonunion was evident in control animals. Collectively, these findings demonstrate that ultrasound-mediated gene delivery to endogenous mesenchymal progenitor cells can effectively treat nonhealing bone fractures in large animals, thereby addressing a major orthopedic unmet need and offering new possibilities for clinical translation.

CT-guided biopsy of bone and soft-tissue lesions: role of on-site immediate cytologic evaluation.

PURPOSE To assess the impact of on-site immediate cytologic assessment (ICA) on the diagnostic success rate of computed tomography (CT)-guided percutaneous needle biopsy (PNB) of musculoskeletal lesions and the long-term outcome in inconclusive PNB findings. MATERIALS AND METHODS A total of 299 CT-guided PNBs of musculoskeletal lesions performed between January 1997 and December 2009 were retrospectively reviewed. The lesions were categorized by their morphology, location, and size, and by biopsy type. The diagnostic success rates, impact of ICA, and outcome in inconclusive PNBs were studied, with final histopathologic findings and/or clinical follow-up as a reference. RESULTS The overall diagnostic success rate of PNBs was 72.9% (218 of 299). The success rate increased with larger lesions (> 2 cm to 4 cm; P = .009). Biopsies performed with ICA had a higher success rate (77.0% vs 63.3%; P = .015). PNBs had inconclusive results in 109 of 299 cases (36.5%). In 66 of these, repeat open biopsy or clinical follow-up demonstrated 19 malignant/aggressive lesions (28.8%) and 47 benign/nonaggressive lesions (71.2%). CONCLUSIONS CT-guided PNB had a satisfactory success rate, which significantly increased when performed with ICA. Inconclusive results in PNB were most frequently associated with benign findings during further workup.

Use of 3D Prints to Compare the Efficacy of Three Different Calcaneal Osteotomies for the Correction of Heel Varus

Background: Cavovarus deformity of the hindfoot is typically caused by neurologic disorders. Multiple osteotomies have been described for the correction of varus deformity but without clinical comparison. In this study, we used 18 identical 3-dimensional (3D) prints of a patient with heel varus to compare the operative correction obtained with Dwyer, oblique, and Z osteotomies. Methods: A computed tomography (CT) scan of a patient with heel varus was used to create 18 identical 3D prints of the talus, calcaneus, and cuboid. Coordinate frames were added to the talus and calcaneus to evaluate rotation. The prints were then divided into 3 groups of 6 models each. A custom jig precisely and accurately replicated each osteotomy. Following the simulated operations, cut models were CT scanned and compared with 6 uncut models. Measurements were calculated using multiplanar reconstruction image processing. An analysis of variance (ANOVA) was performed on the initial data to determine significant differences among the measured variables. A Tukey Studentized range test was run to compare variables that showed statistically significant differences using the ANOVA. Results: The coronal angle of the Dwyer and oblique osteotomies was significantly less than that of the Z osteotomy (P < .05). The axial angle, lateral displacement, and calcaneal shortening of the uncut model and Z osteotomy were significantly less than the Dwyer and oblique osteotomies. Conclusions: Dwyer, oblique, and Z osteotomies did not create either lateral translation or coronal rotation without the addition of a lateralizing slide or rotation of the posterior tuberosity. Clinical Relevance: Dwyer and oblique osteotomies would be best suited for mild deformity, yet the amount of calcaneal shortening must be acknowledged. A Z osteotomy is a complex procedure that has the capability of correcting moderate-severe coronal plane rotation but fails to provide lateralization of the pull of the Achilles insertion.

Quantitative chemical exchange saturation transfer MRI of intervertebral disc in a porcine model.

Previous studies have associated low pH in intervertebral discs (IVDs) with discogenic back pain. The purpose of this study was to determine whether quantitative CEST (qCEST) MRI can be used to detect pH changes in IVDs in vivo.

Ultrasound-mediated transfection of endogenous stem cells for regenerative medicine

The oscillation of microbubbles has long been hypothesized to provide the opportunity to enhance gene delivery as a result of changes in membrane permeability; however, translationally-relevant therapeutic protocols have not yet been realized. We sought to develop and validate a protocol to transfect endogenous mesenchymal stem cells (MSCs) via the local injection of plasmids and microbubbles and the application of ultrasound. We apply this therapy in a pre-clinical model to solve an important clinical problem — that of healing segmental bone defects. More than two million bone-grafting procedures are performed each year using autografts or allografts and these standard of care therapies have substantial disadvantages.

Enhanced ACL Graft Incorporation by Novel Minimally Invasive Activation of Endogenous Stem Cells

Objectives: The ultimate healing of a ligament graft to bone is a lengthy process that results in reparative tissue that is distinctly different from a native ligament insertion. This known structural aberration results in inferior biomechanical properties and can contribute significantly to recurrent injury as well as compromised function. Thus, technology allowing for accelerated biologic incorporation as well as the recapitulation of a native insertion would be of great benefit to patients. We hypothesized that the treatment of anterior cruciate ligament (ACL) reconstruction bone tunnels with bone morphogenetic protein (BMP) DNA combined with a pulse of ultrasound (US) energy would lead to activation of endogenous stem cells and result in enhanced graft incorporation. Methods: Soft tissue allograft ACL reconstruction was performed in nine mini-pigs using cortical screw post fixation. A collagen scaffold was added to the terminus of each tendon graft limb contained within the corresponding bone tunnel. On post-operative day 14, a lipid microsphere solution containing DNA encoding either green fluorescence protein (GFP, n=3 pigs) or BMP-6 (n=6 pigs) was delivered into the bone tunnels percutaneously under fluoroscopic guidance. The bone tunnels in the US treated group were then immediately treated with a transcutaneous US energy pulse at the site of the bone tunnels, whereas the control group did not receive US delivery. At five days post-treatment the cells occupying the bone tunnels of the GFP treated pigs (n=3) were harvested and subjected to fluorescence-activated cell sorting (FACS) analysis to assess for expression of GFP as well as known mesenchymal stem cell (MSC) markers (CD29, CD44, CD90). Six weeks post-treatment the BMP/US treated pigs (n=3) and control pigs (n=3) were sacrificed and their knee joints were scanned using microCT. Biomechanical testing of anterior-posterior (AP) knee laxity was performed via application of sinusoidal AP-directed shear loads for 12 cycles. Load to failure was assessed by removal of the joint capsule, menisci, collateral ligaments, and the PCL leaving only the ACL graft intact. The tibia and femur were then mounted on a universal material testing machine with a 5kN load cell and distracted until failure of the ACL graft or graft-bone interface. Results: FACS analysis done 5 days after GFP gene delivery showed that 40-50% of the cells occupying the US treated bone tunnels expressed GFP and this was significantly more than the cells in untreated bone tunnels (p< 0.05). In addition, 12-22% of the cells in the bone tunnels expressed MSC markers. Quantification of bone volume in ACL reconstruction tunnels showed significantly higher values in BMP-6/US treated animals (fig 1A,B,C; *p<0.05, t-test). AP laxities at ±20N of BMP-6/US treated pigs were lower than untreated pigs (fig 1D). The linear stiffness (fig 1E) and maximum load to failure (fig 1F) were both significantly higher than untreated pigs, demonstrating stronger graft-bone integration among the treated animals. (*p<0.05, t-test). Conclusion: Endogenous stem cell gene expression can be altered in a large animal model via novel minimally invasive techniques and this can result in enhanced ligament biomechanical properties. Minimally invasive biologic technology such as this would likely be of significant benefit to the treatment of patients undergoing ligament reconstruction procedures and more research regarding these technologies is certainly warranted.

Bisphosphonate-Related Atypical Femur Fractures and Their Radiographic Features

Atypical femoral fractures (AFFs) are a rare, but serious, side effect of bisphosphonate therapy. They occur with minimal trauma and can be even more debilitating than high-trauma subtrochanteric fractures. Classically, these fractures show the early radiographic warning signs of endosteal and periosteal thickening of the subtrochanteric lateral femoral cortex. Subsequently, a transverse fracture line progresses medially until complete fracture. Diagnosis is highly reliant on identification of these findings on X-ray, DXA, or MRI. Nuclear scintigraphy is highly sensitive, but lacks specificity. Optimal screening methods are currently being researched, especially as developing fractures may be entirely asymptomatic.