SPECT/CT and PET/CT for the Evaluation of Persistent or Recurrent Pain After Spine Surgery: A Systematic Review and Case Series.

OBJECTIVE: The differential diagnosis for postoperative back pain is broad, and conventional imaging modalities are not always conclusive. Therefore, we performed a systematic review of the literature and present case studies describing the use of single-photon emission CT (SPECT)/CT or positron emission tomography (PET)/CT in the diagnosis of back pain following spine surgery. METHODS: A systematic review was conducted according to PRISMA guidelines across 5 databases. Relevant keywords included PET/CT, bone SPECT/CT, and pseudarthrosis. The studies were assessed for diagnostic accuracy of the imaging technologies. RESULTS: A total of 2,444 studies were screened, 91 were selected for full-text review, and 21 were ultimately included. Six retrospective studies investigated the use of SPECT/CT with a total sample size of 309 patients. Two of these studies used SPECT/CT to predict screw loosening in over 50% of patients. Eight studies examined the use of 18-fluoride sodium fluoride (18F-NaF) PET/CT. Among these studies, measures of diagnostic accuracy varied but overall demonstrated the ability of 18F-NaF PET/CT to detect screw loosening and pseudarthrosis. Seven studies examined 18F-fluorodeoxyglucose (FDG) PET/CT and supported its utility in the diagnosis of postoperative infections in the spine. CONCLUSIONS: PET/CT and SPECT/CT are useful in the evaluation of postoperative pain of the spine, especially in patients for whom conventional imaging modalities yield inconclusive results. More diagnostic accuracy studies with strong reference standards are needed to compare hybrid imaging to conventional imaging.

Low-Intensity Pulsed Ultrasound Neuromodulation of a Rodent's Spinal Cord Suppresses Motor Evoked Potentials.

OBJECTIVE: Here we investigate the ability of low-intensity ultrasound (LIUS) applied to the spinal cord to modulate the transmission of motor signals. METHODS: Male adult Sprague-Dawley rats (n = 10, 250-300 g, 15 weeks old) were used in this study. Anesthesia was initially induced with 2% isoflurane carried by oxygen at 4 L/min via a nose cone. Cranial, upper extremity, and lower extremity electrodes were placed. A thoracic laminectomy was performed to expose the spinal cord at the T11 and T12 vertebral levels. A LIUS transducer was coupled to the exposed spinal cord, and motor evoked potentials (MEPs) were acquired each minute for either 5- or 10-minutes of sonication. Following the sonication period, the ultrasound was turned off and post-sonication MEPs were acquired for an additional 5 minutes. RESULTS: Hindlimb MEP amplitude significantly decreased during sonication in both the 5- (p < 0.001) and 10-min (p = 0.004) cohorts with a corresponding gradual recovery to baseline. Forelimb MEP amplitude did not demonstrate any statistically significant changes during sonication in either the 5- (p = 0.46) or 10-min (p = 0.80) trials. CONCLUSION: LIUS applied to the spinal cord suppresses MEP signals caudal to the site of sonication, with recovery of MEPs to baseline after sonication. SIGNIFICANCE: LIUS can suppress motor signals in the spinal cord and may be useful in treating movement disorders driven by excessive excitation of spinal neurons.

Multimodal interventions to optimize spinal cord perfusion in patients with acute traumatic spinal cord injuries: a systematic review.

OBJECTIVE: The authors systematically reviewed current evidence for the utility of mean arterial pressure (MAP), intraspinal pressure (ISP), and spinal cord perfusion pressure (SCPP) as predictors of outcomes after traumatic spinal cord injury (SCI). METHODS: PubMed, Cochrane Reviews Library, EMBASE, and Scopus databases were queried in December 2020. Two independent reviewers screened articles using Covidence software. Disagreements were resolved by a third reviewer. The inclusion criteria for articles were 1) available in English; 2) full text; 3) clinical studies on traumatic SCI interventions; 4) involved only human participants; and 5) focused on MAP, ISP, or SCPP. Exclusion criteria were 1) only available in non-English languages; 2) focused only on the brain; 3) described spinal diseases other than SCI; 4) interventions altering parameters other than MAP, ISP, or SCPP; and 5) animal studies. Studies were analyzed qualitatively and grouped into two categories: interventions increasing MAP or interventions decreasing ISP. The Scottish Intercollegiate Guidelines Network level of evidence was used to assess bias and the Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate confidence in the anticipated effects of each outcome. RESULTS: A total of 2540 unique articles were identified, of which 72 proceeded to full-text review and 24 were included in analysis. One additional study was included retrospectively. Articles that went through full-text review were excluded if they were a review paper (n = 12), not a full article (n = 12), a duplicate paper (n = 9), not a human study (n = 3), not in English (n = 3), not pertaining to traumatic SCI (n = 3), an improper intervention (n = 3), without intervention (n = 2), and without analysis of intervention (n = 1). Although maintaining optimal MAP levels is the current recommendation for SCI management, the published literature supports maintenance of SCPP as a stronger indicator of favorable outcomes. Studies also suggest that laminectomy and durotomy may provide better outcomes than laminectomy alone, although higher-level studies are needed. Current evidence is inconclusive on the effectiveness of CSF drainage for reducing ISP. CONCLUSIONS: This review demonstrates the importance of assessing how different interventions may vary in their ability to optimize SCPP.

Automated prediction of the Thoracolumbar Injury Classification and Severity Score from CT using a novel deep learning algorithm.

OBJECTIVE: Damage to the thoracolumbar spine can confer significant morbidity and mortality. The Thoracolumbar Injury Classification and Severity Score (TLICS) is used to categorize injuries and determine patients at risk of spinal instability for whom surgical intervention is warranted. However, calculating this score can constitute a bottleneck in triaging and treating patients, as it relies on multiple imaging studies and a neurological examination. Therefore, the authors sought to develop and validate a deep learning model that can automatically categorize vertebral morphology and determine posterior ligamentous complex (PLC) integrity, two critical features of TLICS, using only CT scans. METHODS: All patients who underwent neurosurgical consultation for traumatic spine injury or degenerative pathology resulting in spine injury at a single tertiary center from January 2018 to December 2019 were retrospectively evaluated for inclusion. The morphology of injury and integrity of the PLC were categorized on CT scans. A state-of-the-art object detection region-based convolutional neural network (R-CNN), Faster R-CNN, was leveraged to predict both vertebral locations and the corresponding TLICS. The network was trained with patient CT scans, manually labeled vertebral bounding boxes, TLICS morphology, and PLC annotations, thus allowing the model to output the location of vertebrae, categorize their morphology, and determine the status of PLC integrity. RESULTS: A total of 111 patients were included (mean ± SD age 62 ± 20 years) with a total of 129 separate injury classifications. Vertebral localization and PLC integrity classification achieved Dice scores of 0.92 and 0.88, respectively. Binary classification between noninjured and injured morphological scores demonstrated 95.1% accuracy. TLICS morphology accuracy, the true positive rate, and positive injury mismatch classification rate were 86.3%, 76.2%, and 22.7%, respectively. Classification accuracy between no injury and suspected PLC injury was 86.8%, while true positive, false negative, and false positive rates were 90.0%, 10.0%, and 21.8%, respectively. CONCLUSIONS: In this study, the authors demonstrate a novel deep learning method to automatically predict injury morphology and PLC disruption with high accuracy. This model may streamline and improve diagnostic decision support for patients with thoracolumbar spinal trauma.

Advances in monitoring for acute spinal cord injury: a narrative review of current literature.

Spinal cord injury (SCI) is a devastating condition that affects about 17,000 individuals every year in the United States, with approximately 294,000 people living with the ramifications of the initial injury. After the initial primary injury, SCI has a secondary phase during which the spinal cord sustains further injury due to ischemia, excitotoxicity, immune-mediated damage, mitochondrial dysfunction, apoptosis, and oxidative stress. The multifaceted injury progression process requires a sophisticated injury-monitoring technique for an accurate assessment of SCI patients. In this narrative review, we discuss SCI monitoring modalities, including pressure probes and catheters, micro dialysis, electrophysiologic measures, biomarkers, and imaging studies. The optimal next-generation injury monitoring setup should include multiple modalities and should integrate the data to produce a final simplified assessment of the injury and determine markers of intervention to improve patient outcomes.

Augmented Reality in Spine Surgery: A Narrative Review.

Augmented reality (AR) navigation refers to novel technologies that superimpose images, such as radiographs and navigation pathways, onto a view of the operative field. The development of AR navigation has focused on improving the safety and efficacy of neurosurgical and orthopedic procedures. In this review, the authors focus on 3 types of AR technology used in spine surgery: AR surgical navigation, microscope-mediated heads-up display, and AR head-mounted displays. Microscope AR and head-mounted displays offer the advantage of reducing attention shift and line-of-sight interruptions inherent in traditional navigation systems. With the U.S. Food and Drug Administration's recent clearance of the XVision AR system (Augmedics, Arlington Heights, IL), the adoption and refinement of AR technology by spine surgeons will only accelerate.

Endothelial/Mesenchymal Stem Cell Crosstalk Within Bioprinted Cocultures.

The development of viable tissue surrogates requires a vascular network that sustains cell metabolism and tissue development. The coculture of endothelial cells (ECs) and mesenchymal stem cells (MSCs), the two key players involved in blood vessel formation, has been heralded in tissue engineering (TE) as one of the most promising approaches for scaffold vascularization. However, MSCs may exert both proangiogenic and antiangiogenic role. Furthermore, it is unclear which cell type is responsible for the upregulation of angiogenic pathways observed in EC:MSC cocultures. There is disagreement on the proangiogenic action of MSCs, as they have also been shown to negatively affect the formation of capillary networks. To address these issues, we investigated the regulation of key angiogenic pathways in scaffolds hosting different EC:MSC ratios fabricated through extrusion-based bioprinting. Human ECs were cocultured with either rat or human MSCs, and the regulation of fundamental angiogenic and arteriogenic pathways was analyzed through DNA, gene, and protein expression. The use of a hybrid human/rat coculture system facilitated pinpointing each cell type role in the regulation of specific genes and showed that MSCs exert a dose-dependent inhibitory effect on the EC expression of angiogenic factors within the first 24 h. Within a week of coculture, MSCs exert a proangiogenic effect, as corroborated in human/human bioprinted cocultures. Interestingly, juxtacrine signaling promoted secretion of the angiogenic factor vascular endothelial growth factor in direct cocultures (EC and MSC co-encapsulated), while paracrine signaling encouraged secretion of the arteriogenic factor platelet-derived growth factor in indirect cocultures (adjacent bioprinting of EC-laden and MSC-laden scaffolds). Overall, the use of a bioprinted system to elucidate EC:MSC interplay allows rapid leveraging of the data for novel vascular TE applications. Despite the transitory negative effect early in the culture, MSC presence is necessary for the regulation of pathways involved in arteriogenesis. With further validation in vivo, this study provides a possible explanation to the controversial findings present in literature and shows how MSC effect on angiogenic pathway regulation mimics the dynamics of blood vessel formation reported in literature and normally occurring in vivo. Impact Statement The coculturing of endothelial cells (ECs) and mesenchymal stem cells (MSCs) holds great promise in tissue engineering for the development of prevascularized tissue constructs. Yet, different studies report conflicting results on the role of MSCs, which can either support or inhibit vasculature formation. Furthermore, it is unclear how each cell type modulates distinct pathways involved in angiogenesis when cocultured. Using bioprinted hybrid coculture systems, we show that MSCs have both a time- and dose-dependent effect on the gene and protein expression of key angiogenic and arteriogenic factors by ECs. These findings, obtained in translationally relevant setup, can readily inform the design of vascularized scaffolds.