Sheen-Woo Lee

Magnetic resonance reporter gene imaging.

Molecular imaging has undergone an explosive advancement in recent years, due to the tremendous research efforts made to understand and visualize biological processes. Molecular imaging by definition assesses cellular and molecular processes in living subjects, with the targets of following metabolic, genomic, and proteomic events. Furthermore, reporter gene imaging plays a central role in this field. Many different approaches have been used to visualize genetic events in living subjects, such as, optical, radionuclide, and magnetic resonance imaging. Compared with the other techniques, magnetic resonance (MR)-based reporter gene imaging has not occupied center stage, despite its superior three-dimensional depictions of anatomical details. In this article, the authors review the principles and applications of various types of MR reporter gene imaging technologies and discuss their advantages and disadvantages.

Candida Septic Arthritis with Rice Body Formation: A Case Report and Review of Literature

Rice body formation in a joint or bursa is a rare condition, and is usually associated with rheumatoid arthritis or tuberculous arthritis. Here we describe a case of multiple rice body formation in a shoulder joint and in adjacent bursae, which was confirmed to be due to septic arthritis by Candida species. To the best of our knowledge, rice body formation in Candida septic arthritis in an immune-competent patient has not been previously reported.

Candida Spondylitis: Comparison of MRI Findings With Bacterial and Tuberculous Causes

OBJECTIVE Candida spondylitis is relatively uncommon and is usually encountered as an opportunistic infection. We analyzed the MRI characteristics of biopsy-proven cases of Candida spondylitis, and compared the findings with bacterial or tuberculous spondylitis. MATERIALS AND METHODS The study included patients with infectious spondylitis who underwent MRI and biopsy from 1998 to 2011 (60 patients; mean age 56 ± 18 years). MR images were analyzed with respect to the number of involved vertebrae, contrast enhancement pattern, signal intensity of spinal inflammatory masses on T2-weighted imaging, paraspinal abscess size, intervertebral disk destruction, subligamentous spread, and skip lesions. The Fisher exact test and analysis of variance were used for statistical analysis. RESULTS There were 10 cases of Candida spondylitis, and 29 and 21 cases of bacterial and tuberculous spondylitis, respectively. On MRI, disk destruction was seen in 50%, 93%, and 30% of Candida, bacterial, and tuberculous cases, respectively. Subligamentous spread of infection was noted in 22%, 10%, and 85%. Paraspinal inflammatory masses were seen in 100%, 100%, and 76%, and abscesses in 100%, 66%, and 90%, of Candida, bacterial, and tuberculous cases, respectively. Paraspinal inflammatory masses contained low T2 signal intensity portions in 80%, 21%, and 67%, and skip lesions were seen in 0%, 10%, and 14%, respectively. Small abscesses were noted in 100%, 76%, and 35% of Candida, bacteria, and tuberculosis infections, respectively. Candida involved 2.3 ± 0.4 vertebrae compared with 2.3 ± 0.9 and 3.0 ± 1.7 in bacterial and tuberculous, respectively. Differences in the three groups were statistically significant (p < 0.05) except for the number of involved vertebrae, and skip lesions. CONCLUSION Candida spondylitis can be suspected when infectious lesions contain low-signal spinal inflammatory masses on T2-weighted imaging, small paraspinal abscesses, and in immunocompromised patients.

Assessment of Collagen-Induced Arthritis Using Cyanine 5.5 Conjugated with Hydrophobically Modified Glycol Chitosan Nanoparticles: Correlation with 18F-Fluorodeoxyglucose Positron Emission Tomography Data

Objective To evaluate the potential and correlation between near-infrared fluorescence (NIRF) imaging using cyanine 5.5 conjugated with hydrophobically modified glycol chitosan nanoparticles (HGC-Cy5.5) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging of collagen-induced arthritis (CIA). Materials and Methods We used 10 CIA and 3 normal mice. Nine days after the injecting collagen twice, microPET imaging was performed 40 minutes after the intravenous injection of 9.3 MBq 18F-FDG in 200 µL PBS. One day later, NIRF imaging was performed two hours after the intravenous injection of HGC-cy5.5 (5 mg/kg). We assessed the correlation between these two modalities in the knees and ankles of CIA mice. Results The mean standardized uptake values of 18F-FDG for knees and ankles were 1.68 ± 0.76 and 0.79 ± 0.71, respectively, for CIA mice; and 0.57 ± 0.17 and 0.54 ± 0.20 respectively for control mice. From the NIRF images, the total photon counts per 30 mm2 for knees and ankles were 2.32 ± 1.54 × 105 and 2.75 ± 1.51 × 105, respectively, for CIA mice, and 1.22 ± 0.27 × 105 and 0.88 ± 0.24 × 105, respectively, for control mice. These two modalities showed a moderate correlation for knees (r = 0.604, p = 0.005) and ankles (r = 0.464, p = 0.039). Moreover, both HGC-Cy5.5 (p = 0.002) and 18F-FDG-PET (p = 0.005) imaging also showed statistically significant differences between CIA and normal mice. Conclusion NIRF imaging using HGC-Cy5.5 was moderately correlated with 18F-FDG-PET imaging in the CIA model. As such, HGC-Cy5.5 imaging can be used for the early detection of rheumatoid arthritis.

Radiation exposure for fluoroscopy-guided lumbosacral epidural steroid injections: comparison of the transforaminal and caudal approaches.

Study Design: A retrospective investigation. Objective: We evaluated and compared the radiation exposure caused by using the fluoroscopy-guided transforaminal and caudal approaches of lumbosacral epidural steroid injection (ESI). Summary of Background Data: Only a few studies focused on the radiation exposure to patients who underwent lumbosacral ESI for pain management. Materials and Methods: A total of 228 patients (83 males, 145 females; mean age, 63.3 y) who received lumbosacral ESI were included. Transforaminal ESI was performed in 181 patients (67 males, 114 females; mean age, 61.3 y) and caudal ESI was used in 47 patients (16 males, 31 females; mean age, 69.7 y). All ESIs were performed under a single-plane fluoroscopic guidance by 1 musculoskeletal radiologist. The kerma-area product (KAP) and fluoroscopy time were recorded in all patients. Both measurements were correlated and compared for each approach. Results: KAP was 3.02–1048.2 &mgr;Gy m2 (mean, 101.7 &mgr;Gy m2; median, 67.8 &mgr;Gy m2) for transforaminal ESI and 16.0–604.5 &mgr;Gy m2 (mean, 101.8 &mgr;Gy m2; median, 54.6 &mgr;Gy m2) for caudal ESI. The fluoroscopy time was 11–161 seconds for transforaminal ESI (mean, 36.0 s; median, 29 s) and 4–78 seconds (mean, 18.2 s; median, 13 s) for caudal ESI. KAP and fluoroscopy time were positively correlated for each approach (P<0.001). Fluoroscopy time was significantly longer for transforaminal ESI (correlation coefficient=−0.77, P=0.000). After correction for the fluoroscopy time, KAP was less in transforaminal ESI than in caudal ESI (correlation coefficient=0.74, P=0.000). Conclusions: The longer the fluoroscopy time, the greater the KAP in both transforaminal and caudal ESIs. The fluoroscopy time for transforaminal ESI was longer than that for caudal ESI. However, KAP of transforaminal ESI was less than that of the caudal ESI, after being corrected for the length of fluoroscopy time.

Fracture Healing Effects of Locally-Administered Adipose Tissue-Derived Cells

Purpose Although the applications of adipose tissue-derived cells (ADCs) in regenerative medicine have been investigated, the role of ADCs in fracture healing remains unclear. In this study, we examined the fracture-healing effects and survival of transplanted ADCs using micro-computed tomography (CT) and bioluminescence imaging (BLI). Materials and Methods Luciferase-expressing ADCs were suspended in solubilized basement membrane preparation (SBMP) and xenografted on defects in the right femur of nude mice (n=5). SBMP alone was grafted on a defect in the contralateral femur. Serial in vivo micro-CT and BLI were performed for 20 days. Ex vivo BLI images of both femurs were obtained. Differences in the Hounsfield unit (HU), HUratio, and luciferase activities were compared using Wilcoxon signed-rank tests and non-parametric longitudinal analyses (p<0.05). Results In vivo BLI revealed a signal drop on day 2, reconstitution on day 5, and continuous decrement thereafter. Ex vivo BLI revealed residual activity in the ADC-implanted and adjacent areas. No activity was detected in the contralateral femur. The overall increment rate of normalized HUs was higher for ADC-treated femurs than for SBMP-treated femurs. Cell migration to distant injury sites was not detected. Conclusion Enhanced bone density in the implant area suggests that ADCs have fracture-healing effects.

Using three-dimensional isotropic SPACE MRI to detect posterolateral corner injury of the knee.

Background Reliable magnetic resonance imaging (MRI) diagnosis is important in cases of posterolateral corner (PLC) injury due to the limitations of physical examination in patients with multi-ligament injury. Purpose To document the appearance of PLC of the knee on three-dimensional (3D) isotropic MR images, and to determine the significance of MRI findings in patients with confirmed posterolateral rotatory instability. Material and Methods Twenty-five patients that underwent surgery for posterolateral instability, and 25 individuals with normal MRI constituted the study cohort. The PLC appearances (popliteofibular, fabellofibular, arcuate ligaments, popliteomeniscal fascicle) were analyzed using 3D isotropic proton density sequence and routine two-dimensional (2D) MRI. In addition, the “fibular cap” sign was evaluated. Statistical analysis was performed using the Chi-square and McNemar’s tests. Results Thickening of popliteofibular, fabellofibular, arcuate ligaments, and popliteomeniscal fascicle was significantly more frequent in the PLC injury group than in the control group (P < 0.05). The sensitivity and specificity of 3D MRI for popliteofibular, fabellofibular, arcuate ligaments, and popliteomeniscal fascicle injury were 63/92%, 54/100%, 46/100%, and 58/92%, respectively. On comparing 3D and 2D images with respect to injury detectability (grade 3 or 4), both modalities visualized injuries, but 3D detected grade 3 or grade 1 rather than grade 4 or 0, respectively. The fibular cap sign was observed significantly more frequently in PLC group, with 58% sensitivity and 100% specificity, and was better observed by 3D than 2D (P < 0.05). Conclusion 3D MRI is a valid modality for detecting PLC abnormalities as it visualizes pathologies in each component and exhibits the positive fibular cap sign.

Comparison of radiation exposure during fluoroscopy-guided transforaminal epidural steroid injections at different vertebral levels.

Objective To estimate and compare radiation exposure during transforaminal fluoroscopy-guided epidural steroid injection (TFESI) at different vertebral levels. Materials and Methods Fluoroscopy-guided TFESI was performed in 181 patients. The patients were categorized into three groups according to the injected lumbosacral nerve level of L2-4, L5, or S1. Fluoroscopy time (FT) and dose area product (DAP) were recorded for all patients; correlations between FT and DAP were determined at each level, and both FT and DAP were compared between the different vertebral levels. Results The numbers of patients who received ESI at L2-4, L5, and S1 were 29, 123, and 29. Mean FT was 44 seconds at L2-4, 33.5 seconds at L5, and 37.7 seconds at S1. Mean DAP was 138.6 µGy·m2 at L2-4, 100.6 µGy·m2 at L5, and 72.1 µGy·m2 at S1. FT and DAP were positively correlated in each group (p values < 0.001). FT was significantly shorter at L5 than that at L2-4 (p = 0.004) but was not significantly different between S1 and L2-4 or L5 (p values = 0.286 and 0.532, respectively). DAP was significantly smaller at L5 and S1 than that at L2-4, but L5 and S1 were not significantly different. After correcting for FT, DAP was significantly smaller at S1 than that at either L2-4 or L5 (p values = 0.001 and 0.010). Conclusion The radiation dose was small during a single procedure of ESI and showed differences between different lumbosacral spine levels.

Successful treatment of chronic knee pain following localization by a sigma-1 receptor radioligand and PET/MRI: a case report

Background The ability to accurately diagnose and objectively localize pain generators in chronic pain sufferers remains a major clinical challenge since assessment relies on subjective patient complaints and relatively non-specific diagnostic tools. Developments in clinical molecular imaging, including advances in imaging technology and radiotracer design, have afforded the opportunity to identify tissues involved in pain generation based on their pro-nociceptive condition. The sigma-1 receptor (S1R) is a pro-nociceptive receptor upregulated in painful, inflamed tissues, and it can be imaged using the highly specific radioligand 18F-FTC-146 with PET. Case presentation A 50-year-old woman with a 7-year history of refractory, left-knee pain of unknown origin was referred to our pain management team. Over the past several years, she had undergone multiple treatments, including a lateral retinacular release, radiofrequency ablation of a peripheral nerve, and physical therapy. While certain treatments provided partial relief, her pain would inevitably return to its original state. Using simultaneous positron emission tomography/magnetic resonance imaging (PET/MRI) with the novel radiotracer 18F-FTC-146, imaging showed increased focal uptake of 18F-FTC-146 in the intercondylar notch, corresponding to an irregular but equivocal lesion identified in the simultaneously acquired MRI. These imaging results prompted surgical removal of the lesion, which upon resection was identified as an inflamed, intraarticular synovial lipoma. Removal of the lesion relieved the patient’s pain, and to date the pain has not recurred. Conclusion We present a case of chronic, debilitating knee pain that resolved with surgery following identification of the pathology with a novel clinical molecular imaging approach that detects chronic pain generators at the molecular and cellular level. This approach has the potential to identify and localize pain-associated pathology in a variety of chronic pain syndromes.

Effect of local treatment with adipose tissue-derived mesenchymal stem cells in the early tumorigenesis of osteosarcoma

There are conflicting data describing the effect of mesenchymal stem cells (MSCs) on tumorigenesis. The present study aimed to determine the survival rate and effect of adipose tissue-derived MSCs (ADMSCs) in tumor growth using bioluminescence imaging (BLI) and ultrasound (US) in an osteosarcoma xenograft model. Firefly luciferase-expressing ADMSCs combined with the osteosarcoma cell line UMR-106 in 4 different proportions (5, 10, 15 and 25%, named G1-G4, respectively) were xenografted into the right flanks of nude mice. The same number of UMR-106 cells was inoculated into the contralateral side of each mouse. Serial bioluminescence images were captured over 16 days to monitor the presence of ADMSCs in each group of 5 animals. The tumor volume was measured by ultra-high resolution US, and the tumor volume ratio (AMDSC mixed xenograft/control xenograft) was obtained to evaluate the effect of AMDSCs on tumor growth. Immunohistochemistry was performed to confirm the distribution of residual AMDSCs in the tumor. In G1, G2 and G3, the suppression of tumor growth by AMDSCs was noted in 2/5, 4/5 and 4/5 mice, respectively. However, accelerated tumor growth was noted in G4, which had the highest proportion of ADMSCs. The tumor volume ratio was significantly lower in G2 and G3 compared to G4, by Mann-Whitney U test (P=0.0159). Bioluminescence images demonstrated a serial decrement of the reporter gene for ADMSCs in the tumor mass without evidence of proliferation. Immunohistochemistry staining revealed minimal residual ADMSCs in the tumor periphery. Taken together, our data revealed that direct inoculation of ADMSCs into a tumor xenograft caused the death of the majority of ADMSCs in the tumor mass. Furthermore, relatively low proportions of ADMSCs suppressed the growth of osteosarcoma, while higher proportions showed a tumor-promoting effect.