Fluorescence-based endoscopic imaging of Thomsen-Friedenreich antigen to improve early detection of colorectal cancer.

Thomsen-Friedenreich (TF) antigen belongs to the mucin-type tumor-associated carbohydrate antigen. Notably, TF antigen is overexpressed in colorectal cancer (CRC) but is rarely expressed in normal colonic tissue. Increased TF antigen expression is associated with tumor invasion and metastasis. In this study, we sought to validate a novel nanobeacon for imaging TF-associated CRC in a preclinical animal model. We developed and characterized the nanobeacon for use with fluorescence colonoscopy. In vivo imaging was performed on an orthotopic rat model of CRC. Both white light and fluorescence colonoscopy methods were utilized to establish the ratio-imaging index for the probe. The nanobeacon exhibited specificity for TF-associated cancer. Fluorescence colonoscopy using the probe can detect lesions at the stage which is not readily confirmed by conventional visualization methods. Further, the probe can report the dynamic change of TF expression as tumor regresses during chemotherapy. Data from this study suggests that fluorescence colonoscopy can improve early CRC detection. Supplemented by the established ratio-imaging index, the probe can be used not only for early detection, but also for reporting tumor response during chemotherapy. Furthermore, since the data obtained through in vivo imaging confirmed that the probe was not absorbed by the colonic mucosa, no registered toxicity is associated with this nanobeacon. Taken together, these data demonstrate the potential of this novel probe for imaging TF antigen as a biomarker for the early detection and prediction of the progression of CRC at the molecular level.

Pedicle Screw Placement Using Intraoperative Computed Tomography and Computer-Aided Spinal Navigation Improves Screw Accuracy and Avoids Postoperative Revisions: Single-Center Analysis of 1400 Pedicle Screws.

OBJECTIVE: Intraoperative computed tomography and navigation (iCT-Nav) is increasingly used to aid spinal instrumentation. We aimed to document the accuracy and revision rate of pedicle screw placement across many screws placed using iCT-Nav. We also assess patient-level factors predictive of high-grade pedicle breach. METHODS: Medical records of patients who underwent iCT-Nav pedicle screw placement between 2015 and 2017 at a single center were retrospectively reviewed. Screw placement accuracy was individually assessed for each screw using the 2-mm incremental grading system for pedicle breach. Predictors of high-grade (>2 mm) breach were identified using multiple logistic regression. RESULTS: In total, 1400 pedicle screws were placed in 208 patients undergoing cervicothoracic (29; 13.9%), thoracic (30; 14.4), thoracolumbar (19; 9.1%) and lumbar (130; 62.5%) surgeries. iCT-Nav afforded high-accuracy screw placement, with 1356 of 1400 screws (96.9%) being placed accurately. In total, 37 pedicle screws (2.64%) were revised intraoperatively during the index surgery across 31 patients, with no subsequent returns to the operating room because of screw malpositioning. After correcting for potential confounders, males were less likely to have a high-grade breach (odds ratio [OR] 0.21; 95% confidence interval [CI] 0.10-0.59, P = 0.003) whereas lateral (OR 6.21; 95% CI 2.47-15.52, P < 0.001) or anterior (OR 5.79; 95% CI2.11-15.88, P = 0.001) breach location were predictive of a high-grade breach. CONCLUSIONS: iCT-Nav with postinstrumentation intraoperative imaging is associated with a reduced need for costly postoperative return to the operating room for screw revision. In comparison with studies of navigation without iCT where 1.5%-1.7% of patients returned for a second surgery, we report 0 revision surgeries due to screw malpositioning.

Objective Indirect Assessment of Transverse Ligament Competence Using Quantitative Analysis of 3-Dimensional Segmented Flexion-Extension Computed Tomography Scan.

OBJECTIVE: Assessment of transverse ligament (TL) competence in patients with suspected atlantoaxial instability is performed via indirect radiograph measurements or direct TL visualization on magnetic resonance imaging (MRI). Interpretation of these images can be limited by unique patient anatomy or imaging technique variability. We report a novel technique for evaluating TL competence using flexion-extension computed tomography (feCT) scan with 3-dimensional (3D) segmentation and quantitative analysis. METHODS: feCT scans of 11 patients were segmented to create 3D surface models. Six patients with atlantoaxial pathology were evaluated for possible instability based on clinical examination and imaging findings. The other 5 patients had no clinical or imaging evidence of atlantoaxial injury. Dynamic atlantodental interval (ADI) was calculated using point-to-point voxel changes between flexion and extension 3D models. Magnitude and direction of ADI changes were quantified and compared with available cervical spine flexion-extension radiograph and/or MRI findings. RESULTS: In the 5 patients without evidence of atlantoaxial injury, 94.3% of ADI vector changes were <3.0 mm. In the 3 patients with atlantoaxial pathology but TL competence, 92.4% of ADI vector changes were <3.0 mm. In the 3 patients with atlantoaxial pathology and TL incompetence, only 49.1% of ADI vector changes were <3.0 mm. In addition to the significant atlantoaxial subluxation in these 3 patients, there was significant rotational motion compared with the patients with an intact TL. CONCLUSIONS: 3D segmentation and quantitative analysis of feCT scan allow objective indirect assessment of TL integrity. Results are consistent with MRI findings and offer additional biomechanical information regarding the direction and distribution of atlantoaxial motion.

Minimally Invasive Thoracolumbar Corpectomy and Stabilization for Unstable Burst Fractures Using Intraoperative Computed Tomography and Computer-Assisted Spinal Navigation.

BACKGROUND: Minimally invasive surgery using a mini-open lateral retropleural or retroperitoneal approach for corpectomy is a well-described procedure for treating unstable thoracolumbar burst fractures. Most surgeons have incorporated fluoroscopy for localization and determination of hardware placement accuracy; however, the utility of computer-assisted image-guided spinal navigation has not been well described. We report a series of mini-open lateral approach thoracolumbar corpectomy cases using either fluoroscopy or intraoperative computed tomography (iCT) with computer-assisted navigation and discuss the technical nuances and advantages of using iCT with navigation versus fluoroscopy. METHODS: A retrospective review and analysis was performed of the cases of 20 patients with thoracolumbar burst fractures surgically managed via mini-open lateral corpectomy with fluoroscopy (2013-2015) or iCT navigation (2015-2017). The surgical outcomes were evaluated by the estimated blood loss, operative time, hospital stay, and need for revision. The clinical outcomes were evaluated using the numerical rating scale pain score. Radiographic outcomes were assessed with follow-up CT scans. The results were statistically analyzed using the Wilcoxon-Mann-Whitney test. RESULTS: The mean follow-up period was 13.4 months for the fluoroscopy group and 14.7 months for the iCT group. No surgical complications developed and no revisions were required. No statistically significant differences were found between the groups in surgical or clinical outcomes. However, the radiation exposure to the surgeons was significantly less with the iCT group (P < 0.003). CONCLUSIONS: The use of iCT with spinal navigation for mini-open lateral corpectomy for thoracolumbar burst fractures yields perioperative and clinical outcomes comparable to those using traditional fluoroscopy, with decreased radiation exposure to surgeons.

Convergent synthesis and evaluation of (18)F-labeled azulenic COX2 probes for cancer imaging.

The overall objectives of this research are to (i) develop azulene-based positron emission tomography (PET) probes and (ii) image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel (18)F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8 + 2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional (18)F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an (18)F labeling strategy that employed a much milder phosphate buffer. The (18)F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further investigation.