Y.C. Choi

The role of 18F-fluorodeoxyglucose–positron emission tomography in the assessment of disease activity in patients with Takayasu arteritis

OBJECTIVE The assessment of disease activity in Takayasu arteritis (TA) is difficult in clinical situations because clinical symptoms and laboratory parameters do not always reflect the actual inflammation of the arterial wall. We undertook this study to comprehensively investigate the role of (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of disease activity in patients with TA. METHODS We performed a retrospective chart review of 53 FDG-PET scans in 38 patients with TA. We measured (18) F-fluorodeoxyglucose ((18) F-FDG) accumulation in the vascular wall of the large vessel using semiquantitative (visual grade) and quantitative (standard uptake value intensity) analyses. Clinical disease activity was evaluated based on the National Institutes of Health criteria for active TA, and erythrocyte sedimentation rates (ESRs) and C-reactive protein (CRP) levels were measured. RESULTS At baseline, active vascular (18) F-FDG uptake (visual grade ≥2) was observed in 18 of 24 patients with active disease and in 5 of 14 patients with inactive disease. There was a significant association between clinical disease activity and disease activity judged by FDG-PET (P = 0.008). Visual grade, standard uptake value intensity, and the number of vascular lesions with active (18) F-FDG uptake were significantly higher in patients with active disease and correlated well with the ESR and CRP levels. In 15 followup FDG-PET scans, the changes in visual grade, areas of active vascular (18) F-FDG uptake, and standard uptake value intensity reflected changes in clinical disease activity. CONCLUSION (18) F-FDG uptake was associated with clinical disease activity and markers of inflammation, and FDG-PET reflected changes in clinical disease activity in patients with TA. FDG-PET may be a useful tool for aiding in the assessment of disease activity in patients with TA.

Visually Discernible [18F]Fluorodeoxyglucose Uptake in Papillary Thyroid Microcarcinoma: A Potential New Risk Factor

CONTEXT A significant number of papillary thyroid microcarcinomas (PTMCs), despite excellent prognosis, show aggressive features such as extrathyroidal extension (EE) and lymph node metastasis (LNM) that may not always be detected preoperatively or intraoperatively. The relapse rate appears also substantial. OBJECTIVE To assess the value of [(18)F]fluorodeoxyglucose (FDG) uptake in PTMC as a potential risk factor for preoperative risk stratification. METHODS This retrospective study included 87 patients (17 males and 70 females; mean age = 51.2 yr, range 29-74 yr) with a unifocal PTMC who underwent preoperative FDG-positron emission tomography (PET)/computed tomography (CT)and total thyroidectomy and central lymph node dissection. Statistical analyses were performed to compare the gender, age, tumor size, and FDG uptake in PTMC with the presence of histopathologically proven EE and central LNM (cLNM). RESULTS Of the 87 patients, 44 (51%) had EE, and 27 (31%) had cLNM. PET/CT showed visually discernible FDG uptake in 46 PTMCs (53%). FDG positivity of PTMCs was the only significant variable correlated with both EE and cLNM; there was a significant difference in the prevalence of both EE (70 vs. 29%) and cLNM (41 vs. 19.5%) between the FDG-positive and FDG-negative groups. In contrast, other already known risk factors, i.e. gender, age, and size, showed a correlation with only one or neither of EE and cLNM. CONCLUSION The results indicate that visual FDG positivity in PTMCs is a potential risk factor that can be useful for preoperative risk stratification. Prospective studies would be warranted to assess the long-term benefit and cost effectiveness of preoperative FDG-PET/CT.

Physiologic 18F-FDG Uptake in the Fallopian Tubes at Mid Cycle on PET/CT

We observed bilateral pelvic foci of 18F-FDG uptake (BiPF) exclusively in females—a finding not previously reported—and assessed the frequency, anatomic localization, and clinical significance of the uptake. Methods: On 18F-FDG PET/CT and coregistered contrast-enhanced CT scans of 159 females (age, 16–81 y), the presence of BiPF and their location were evaluated. The findings were correlated with the age and menstrual history of the patient. Results: BiPF were seen in 14 (22%) of 63 patients up to 53 y old, predominantly at mid menstrual cycle, and were best coregistered to the fallopian tubes on contrast-enhanced CT. None of 96 patients older than 53 y showed BiPF. Conclusion: Fallopian 18F-FDG uptake was seen predominantly in premenopausal women at mid menstrual cycle. This finding is in accordance with known cyclic changes of fallopian tubes in response to ovarian hormones and may be the first, to our knowledge, imaging evidence revealing the influence of estrogen on the fallopian tubes.

Imaging Capabilities of the Inveon SPECT System Using Single-and Multipinhole Collimators

The Inveon small-animal SPECT system comes with several types of multipinhole collimator plates. We evaluate here the performance measurements of the Inveon SPECT system using 6 different collimators: 3 dedicated for mouse imaging and 3 for rat imaging. Methods: The measured performance parameters include the sensitivity, the spatial resolution using line sources, the ultra-micro Derenzo phantom, the recovery coefficient and the noise measurements using the National Electrical Manufacturers Association NU-4 image quality phantom, obtained with the 2 reconstruction algorithms available with the Inveon Acquisition Workplace, version 1.5—the 3-dimensional ordered-subset expectation maximization (3DOSEM) and the 3-dimensional maximum a posteriori (3DMAP). Further, the overall performance of the system is illustrated by an animal experiment. Results: The results show that the Inveon SPECT scanner offers a spatial resolution, measured at the center of the field of view, ranging from 0.6 to 1 mm with the collimator plates dedicated to mouse imaging and from 1.2 to less than 2 mm with rat collimator plates. The system sensitivity varies from 29 to 404 cps/MBq for mouse collimators and from 53 to 175 cps/MBq for rat collimators. The image quality study showed that 3DMAP allows better noise reduction while preserving the recovery coefficient, compared with other regularization strategies such as the premature termination of the 3DOSEM reconstruction or 3DOSEM followed by gaussian filtering. Conclusion: The acquisition parameters, such as the collimator set and the radius of rotation, offer a wide range of possibilities to apply to a large number of biologic studies. However, special care must be taken because this increase in sensitivity can be offset by image degradation, such as image artifacts caused by projection overlap and statistical noise due to a higher number of iterations required for convergence. 3DMAP allowed better noise reduction while maintaining relatively constant recovery coefficients, as compared with other reconstruction strategies.

D.P.10 Whole-genome analysis in Korean patients with autoimmune myasthenia gravis

Abstract The underlying cause of myasthenia gravis is unknown, although there is probably a genetic component to it. We sought to identify the genetic variants associated with an increased or decreased risk of developing myasthenia gravis in the Korean Multicenter MG Cohort samples. To find new genetic targets that are related to autoimmune myasthenia gravis, a whole genome-based SNP analysis was performed using an Axiom Genome-Wide ASI 1 Array plate containing 598,375 SNPs and samples from 109 MG patients and 150 neurologically normal controls. The p values of association between these SNPs and autoimmune myasthenia gravis were calculated in all the available genetic modes such as allele, dominant, recessive, and co-dominant mode using (1) MG and Control, (2) AChR-antibody positive MG and Control, (3) AChR-antibody negative MG and Control, (4) Ocular MG and Control, and (5) Generalized MG and Control samples, respectively. A total of 641 SNPs from five case–control associations showed p values of less than 0.00001. From regional analysis, we selected seven genes (RYR3, CACNA1S, SLAMF1, SOX5, FHOD3, GABRB1, SACS) for further analysis. Fatigue in MG patients was caused not only by abnormal neuromuscular transmission but also by the impairment of excitation–contraction (E–C) coupling. In the process of E–C coupling in skeletal muscle, ryanodine receptor (RyR) and dihydropyridine receptor (DHPR/CACNA1S) function as Ca2+ channels. SLAMF1 leads to IFN- α production of CD4+ T cells. IFN- α production of CD4+ T cells is associated with pathogenesis and immunoregulation of MG. However, speculating the plausibility and the biological significance of these candidate loci is premature because additional genetic data is needed to confirm the notion that these E–C coupling gene or SLAMF1 gene are associated with autoimmune MG. The present study suggests that some genetic polymorphisms might be related to autoimmune myasthenia gravis.

G.P.13 Merosin-deficient congenital muscular dystrophy: A case with immunohistochemical analysis

Abstract Congenital muscular dystrophies (CMDs) are an autosomal recessive and heterogeneous diseases. The CMDs are subclassified into two major categories: merosin positive and deficient. Primary merosin (laminin α 2 chain)-deficient congenital muscular dystrophy (CMD) is a uncommon and severe form of CMD, which is caused by the mutations in the laminin α 2 chain gene. In European studies reported to approximately a half of CMDs are merosin-deficient congenital muscular dystrophy (MDCMD), but it is rarely reported in asian. There were few case reports of MDCMD in Korea, we report a case of MDCMD confirmed by the immunohistochemical analysis of the frozen muscle biopsy. A 7-months-year old female was evaluated for floppy infant syndrome. She was born healthy at IUP 38weeks without perinatal distress. She had neonatal hypotonia, a high serum creatine kinase level of 3130IU/L. Her brain MRI showed a diffuse white matter change on T2WI. There was no family history of muscle weakness or developmental delay. The muscle biopsy showed a marked dystrophic pattern with many endomysial inflammatory cell infiltration. Immunohistochemical staining for dystrophin-C, α -sarcoglycan, β -sarcoglycan and α -dystroglycan proteins were decreased, and for dystrophin-R, dystrophin-N, γ -sarcoglycan, δ -sarcoglycan, dysferlin, caveolin-3 proteins were normal. We report a case of merosin-deficiency congenital muscular dystrophy confirmed by muscle biopsy.

C.P.8 Clinical and pathological characterization of sporadic centronuclear myopathy by DNM2 mutations

Abstract Centronuclear myopathy (CNM) is characterized by a pathological finding of central nuclei. Sporadic or autosomal dominant CNM is linked to a gene encoding dynamin 2 ( DNM2 ) while autosomal recessive and X-linked form are related to BIN1 and MTM1 , respectively. Clinical spectrum of CNM is ranged from severe to mild phenotypes. We are to analyze clinical and pathological features of sporadic CNM patients with or without DNM2 mutations. Six patients were recruited in a basis of central nuclei on more than 30% of muscle fibers. Their clinical features and pathological details were described, and the results from DNM2 sequencing analysis were correlated. Four of the patients had DNM2 mutations scattered over three different domains and have been mostly related to mild phenotype. Four patients had the first symptoms on childhood or early adolescence while the others had developmental delay since infancy. Three of the patients displayed distal dominant weakness whereas other three patients showed proximal dominant weakness. Muscle CT scans reflected the different pattern of muscle involvement. Facial involvement and external ophthalmoplegia were variable but contractures and neck flexor weakness were common. Currently, two patients had respiratory distress, requiring ventilator support. Muscle pathology commonly revealed that a large number of muscle fibers had central nuclei (on 31.6∼100% of muscle fibers). Two of them demonstrated radial arrangement of sarcoplasmic strands, which was corresponded to the electron microscopic findings. This study detected four DNM2 mutations. DNM2 mutations appeared to make differences in clinical and pathological aspects. The patients with mutations showed later disease onset, distal dominant muscle weakness and more typical CNM pathology, such as central nuclei in almost all fibers and radial arrangement of sarcoplasmic strands. Our results may provide some guidance for genetic analyses of CNM.

The role of 18F-fluorodeoxyglucose-positron emission tomography in the assessment of disease activity in patients with Takayasu arteritis: FDG-PET in TA

OBJECTIVE The assessment of disease activity in Takayasu arteritis (TA) is difficult in clinical situations because clinical symptoms and laboratory parameters do not always reflect the actual inflammation of the arterial wall. We undertook this study to comprehensively investigate the role of (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in the assessment of disease activity in patients with TA. METHODS We performed a retrospective chart review of 53 FDG-PET scans in 38 patients with TA. We measured (18) F-fluorodeoxyglucose ((18) F-FDG) accumulation in the vascular wall of the large vessel using semiquantitative (visual grade) and quantitative (standard uptake value intensity) analyses. Clinical disease activity was evaluated based on the National Institutes of Health criteria for active TA, and erythrocyte sedimentation rates (ESRs) and C-reactive protein (CRP) levels were measured. RESULTS At baseline, active vascular (18) F-FDG uptake (visual grade ≥2) was observed in 18 of 24 patients with active disease and in 5 of 14 patients with inactive disease. There was a significant association between clinical disease activity and disease activity judged by FDG-PET (P = 0.008). Visual grade, standard uptake value intensity, and the number of vascular lesions with active (18) F-FDG uptake were significantly higher in patients with active disease and correlated well with the ESR and CRP levels. In 15 followup FDG-PET scans, the changes in visual grade, areas of active vascular (18) F-FDG uptake, and standard uptake value intensity reflected changes in clinical disease activity. CONCLUSION (18) F-FDG uptake was associated with clinical disease activity and markers of inflammation, and FDG-PET reflected changes in clinical disease activity in patients with TA. FDG-PET may be a useful tool for aiding in the assessment of disease activity in patients with TA.