Diagnosis of Seronegative Rheumatoid Arthritis by 68 Ga-FAPI PET/CT.

Early diagnosis of rheumatoid arthritis with the initiation of disease-modifying antirheumatic drugs is important to prevent future disability. Seronegative rheumatoid arthritis lacks the classical immunological markers, thus imposing clinical diagnostic difficulty. In this case, we reported 68 Ga-FAPI PET/CT findings of seronegative rheumatoid arthritis in a 60-year-old lady. This case illustrates how 68 Ga-FAPI PET/CT aids in the diagnosis of seronegative rheumatoid arthritis.

The Complementary Role of PET to Pathology in Differentiating the Primary Origin of a Malignant Skin Nodule from Liver or Lung.

Metastasis from unknown primary is always a challenge because finding the true primary tumor significantly affects subsequent management. We present a case of malignant abdominal wall nodule initially diagnosed as metastasis from hepatocellular carcinoma through excisional biopsy and immunohistochemical (IHC) staining. Dual-tracer positron emission tomography/computed tomography (PET/CT) with 11C-acetate and 18F-FDG, however, showed metabolic findings in favor of metastasis from lung origin, which was finally confirmed by ensuing a lung biopsy with additional IHC stains. This case illustrates the complementary molecular role of PET to pathology, particularly when dual-tracer or multi-tracer PET is used in conjunction with pathology methods for cross referencing and confirmation.

Clinical and neuroimaging markers of neurodegeneration in first-degree relatives of patients with REM sleep behavior disorder with and without isolated rapid eye movement sleep without atonia: A case-control clinical and dopamine PET study.

OBJECTIVES: The current study aimed to examine the neurodegenerative implication of isolated REM sleep without atonia (RSWA) among first-degree relatives of patients with REM sleep behaviour disorder (RBD). METHODS: This cross-sectional case-control study recruited three groups of subjects: First-degree relatives of RBD patients with isolated RSWA (n = 17), first-degree relatives of RBD patients without isolated RSWA (n = 18), and normal controls who did not have any RWSA and family history of RBD (n = 15). Prodromal Parkinson's Disease likelihood ratio by the updated MDS Research Criteria and striatal dopaminergic transmission function of the subjects as assessed by triple-tracer (18F-DOPA, 11C-Raclopride, and 18F-FDG) PET/CT scan were used as proxy markers of neurodegeneration. RESULTS: In contrary to our hypothesis, the three groups did not differ in their pre- or post-striatal dopaminergic transmission function, and their Prodromal Parkinson's Disease likelihood ratio. However, they differed significantly in their frequency of a having first-degree relatives with Parkinson's disease or dementia of Lewy body (first-degree relativess with RSWA vs first degree relatives without RSWA vs normal controls = 58.8% vs 22.2% vs 0%, p = 0.001). CONCLUSION: FDRs of RBD patients with isolated RSWA did not have increased neurodegenerative markers compared to FDRs of RBD patients without isolated RSWA and normal control, despite an paradoxical increase in frequency of Parkinson's disease or dementia of Lewy body among their family compared to FDRs of RBD patients without isolated RSWA. Further longitudinal follow-up study will be needed to ascertain their long-term prognosis.

Reliability of gradient-based segmentation for measuring metabolic parameters influenced by uptake time on 18F-PSMA-1007 PET/CT for prostate cancer.

Purpose: To determine an optimal setting for functional contouring and quantification of prostate cancer lesions with minimal variation by evaluating metabolic parameters on 18F-PSMA-1007 PET/CT measured by threshold-based and gradient-based methods under the influence of varying uptake time. Methods and materials: Dual time point PET/CT was chosen to mimic varying uptake time in clinical setting. Positive lesions of patients who presented with newly diagnosed disease or biochemical recurrence after total prostatectomy were reviewed retrospectively. Gradient-based and threshold-based tools at 40%, 50% and 60% of lesion SUVmax (MIM 6.9) were used to create contours on PET. Contouring was considered completed if the target lesion, with its hottest voxel, was delineated from background tissues and nearby lesions under criteria specific to their operations. The changes in functional tumour volume (FTV) and metabolic tumour burden (MTB, defined as the product of SUVmean and FTV) were analysed. Lesion uptake patterns (increase/decrease/stable) were determined by the percentage change in tumour SUVmax at ±10% limit. Results: A total of 275 lesions (135 intra-prostatic lesions, 65 lymph nodes, 45 bone lesions and 30 soft tissue lesions in pelvic region) in 68 patients were included. Mean uptake time of early and delayed imaging were 94 and 144 minutes respectively. Threshold-based method using 40% to 60% delineated only 85 (31%), 110 (40%) and 137 (50%) of lesions which all were contoured by gradient-based method. Although the overall percentage change using threshold at 50% was the smallest among other threshold levels in FTV measurement, it was still larger than gradient-based method (median: 50%=-7.6% vs gradient=0%). The overall percentage increase in MTB of gradient-based method (median: 6.3%) was compatible with the increase in tumour SUVmax. Only a small proportion of intra-prostatic lesions (<2%), LN (<4%), bone lesions (0%) and soft tissue lesions (<4%) demonstrated decrease uptake patterns. Conclusions: With a high completion rate, gradient-based method is reliable for prostate cancer lesion contouring on 18F-PSMA-1007 PET/CT. Under the influence of varying uptake time, it has smaller variation than threshold-based method for measuring volumetric parameters. Therefore, gradient-based method is recommended for tumour delineation and quantification on 18F-PSMA-1007 PET/CT.

Lower Posterior Cingulate N-Acetylaspartate to Creatine Level in Early Detection of Biologically Defined Alzheimer's Disease.

Alzheimer's disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (1H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (p = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with p < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (r = −0.47, p < 0.001) and tau load (r = −0.51, p < 0.001) and allowed a discrimination of early AD from controls (p < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD.

MRI-based Alzheimer's disease-resemblance atrophy index in the detection of preclinical and prodromal Alzheimer's disease.

Alzheimer's Disease-resemblance atrophy index (AD-RAI) is an MRI-based machine learning derived biomarker that was developed to reflect the characteristic brain atrophy associated with AD. Recent study showed that AD-RAI (≥0.5) had the best performance in predicting conversion from mild cognitive impairment (MCI) to dementia and from cognitively unimpaired (CU) to MCI. We aimed to validate the performance of AD-RAI in detecting preclinical and prodromal AD. We recruited 128 subjects (MCI=50, CU=78) from two cohorts: CU-SEEDS and ADNI. Amyloid (A+) and tau (T+) status were confirmed by PET (11C-PIB, 18F-T807) or CSF analysis. We investigated the performance of AD-RAI in detecting preclinical and prodromal AD (i.e. A+T+) among MCI and CU subjects and compared its performance with that of hippocampal measures. AD-RAI achieved the best metrics among all subjects (sensitivity 0.74, specificity 0.91, accuracy 85.94%) and among MCI subjects (sensitivity 0.92, specificity 0.81, accuracy 86.00%) in detecting A+T+ subjects over other measures. Among CU subjects, AD-RAI yielded the best specificity (0.95) and accuracy (85.90%) over other measures, while hippocampal volume achieved a higher sensitivity (0.73) than AD-RAI (0.47) in detecting preclinical AD. These results showed the potential of AD-RAI in the detection of early AD, in particular at the prodromal stage.

Quantitative Susceptibility Mapping of the Hippocampal Fimbria in Alzheimer's Disease.

BACKGROUND: The fimbria is a small white matter bundle that connects the hippocampus to the rest of the brain. Damage to the hippocampal gray matter is established in Alzheimer's disease (AD), but the hippocampal fimbrial status in the pathogenesis of AD is unclear. AD-related demyelination and iron deposition alter the diamagnetic and paramagnetic composition of tissues, which can be measured by quantitative susceptibility mapping (QSM). HYPOTHESIS: AD is associated with microstructural changes in the fimbria that might be detected by QSM. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: In all, 53 adults comprised of controls (n = 30), subjects with early stage AD (n = 13), and late stage AD (n = 10) who were classified according to their amyloid and tau status and presence of hippocampal atrophy. FIELD STRENGTH / SEQUENCE: 3T; 3D fast-field echo sequence for QSM analysis and 3D T1 -weighted MP-RAGE sequence for anatomical analysis. ASSESSMENT: Segmentation of the left hippocampal fimbria subfield was performed on T1 -weighted images and was applied to the coregistered QSM map for extraction of the mean, median, minimum, and maximum values of QSM. STATISTICAL TESTS: Group comparison of QSM values using analysis of variance (ANOVA) with post-hoc Tukey's test, accuracy of binary differentiation using receiver operating characteristic (ROC), and individual classification using discriminant analysis. RESULTS: QSMmean and QSMmedian values were significantly different among the three groups (P < 0.05) and showed a shifting from negative in the control group to positive in the AD group. The control and early AD subjects, who have normal hippocampal volumes, were differentiated by the QSMmean value (area under the curve [AUC] 0.744, P < 0.05) and the QSMmedian value (AUC 0.782, P < 0.05). Up to 76% of subjects (inclusive of 26 controls and six with early AD) were correctly classified using a model incorporating clinical and radiologic data. DATA CONCLUSION: The fimbria showed higher magnetic susceptibility in AD compared with controls. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Current status of PSMA PET imaging in prostate cancer.

The past decade has witnessed the rising popularity and acceptance of molecular definitions on disease management. Prostate-specific membrane antigen (PSMA), in light of its molecular nature and cytokinetic properties, has rapidly become the target for development of a variety of functional tracers for PET/CT evaluation of prostate cancer. The most commonly used PSMA-binding analog is 68 Ga-labeled PSMA-11, which is now widely applied in both research and clinical settings. Literature data in the recent years have been enriched by a number of meta-analyses and systemic reviews on the evolving role of PSMA PET in primary diagnosis, staging, detection of biochemical recurrence after primary cancer treatment, identification, and significance of oligometastasis, as well as in restaging and treatment monitoring. Being a highly sensitive and reasonably specific molecular tracer, PSMA-binding analogs have a high potential to possess the majority of imaging characteristics required for a variety of management decisions in prostate malignancy.

The role of dopamine dysregulation and evidence for the transdiagnostic nature of elevated dopamine synthesis in psychosis: a positron emission tomography (PET) study comparing schizophrenia, delusional disorder, and other psychotic disorders.

There have been few studies performed to examine the pathophysiological differences between different types of psychosis, such as between delusional disorder (DD) and schizophrenia (SZ). Notably, despite the different clinical characteristics of DD and schizophrenia (SZ), antipsychotics are deemed equally effective pharmaceutical treatments for both conditions. In this context, dopamine dysregulation may be transdiagnostic of the pathophysiology of psychotic disorders such as DD and SZ. In this study, an examination is made of the dopamine synthesis capacity (DSC) of patients with SZ, DD, other psychotic disorders, and the DSC of healthy subjects. Fifty-four subjects were recruited to the study, comprising 35 subjects with first-episode psychosis (11 DD, 12 SZ, 12 other psychotic disorders) and 19 healthy controls. All received an 18F-DOPA positron emission tomography (PET)/magnetic resonance (MR) scan to measure DSC (Kocc;30-60 value) within 1 month of starting antipsychotic treatment. Clinical assessments were also made, which included Positive and Negative Syndrome Scale (PANSS) measurements. The mean Kocc;30-60 was significantly greater in the caudate region of subjects in the DD group (ES = 0.83, corrected p = 0.048), the SZ group (ES = 1.40, corrected p = 0.003) and the other psychotic disorder group (ES = 1.34, corrected p = 0.0045), compared to that of the control group. These data indicate that DD, SZ, and other psychotic disorders have similar dysregulated mechanisms of dopamine synthesis, which supports the utility of abnormal dopamine synthesis in transdiagnoses of these psychotic conditions.

Significant Value of 11C-Acetate and 18F-Fluorodeoxyglucose PET/Computed Tomography on 90Y Microsphere Radioembolization for Hepatocellular Carcinoma.

Pretreatment dual-tracer (18F-fluorodeoxyglucose and 11C-acetate) PET/computed tomography (CT) has potential to predict treatment response for 90Y microsphere radioembolization (RE) in patients with inoperable hepatocellular carcinoma (HCC). Patients with 11C-acetate-avid HCC have a better response to 90Y microsphere RE, and possibly better survival. Pretreatment dual-tracer PET/CT has a significant theranostic value on 90Y microsphere RE in determining target tumor dose for HCCs with different cellular differentiation, metabolic tumor volume, and functioning liver volume, and can be used to prescribe individual injected activity of 90Y microspheres.

Dual-Tracer PET/CT Differentiates 2 Types of Primary Cancers and Metastases in a Patient With Crossed Fused Renal Ectopia.

A patient was found incidentally on dual-tracer (C-acetate [ACT] and F-FDG [FDG]) PET/CT for having crossed fused renal ectopia and 2 types of malignant tumors, colonic carcinoma and renal cell carcinoma (RCC), each having its own characteristic tracer avidity. Multiple liver metastases were also mutually exclusive, with a purely ACT-avid group of metastatic lesions from RCC and another FDG-avid group from colonic carcinoma. Bone and lung metastases, however, could not be readily distinguishable in terms of primary origins. Crossed fused renal ectopia is a rare anomaly, even rarer to have RCC coexisting with a second primary malignancy.

Nosocomial transmission of hepatitis C virus in a liver transplant center in Hong Kong: implication of reusable blood collection tube holder as the vehicle for transmission.

BACKGROUND: A liver transplant recipient developed hospital-acquired symptomatic hepatitis C virus (HCV) genotype 6a infection 14 months post transplant. OBJECTIVE: Standard outbreak investigation. METHODS: Patient chart review, interviews of patients and staff, observational study of patient care practices, environmental surveillance, blood collection simulation experiments, and phylogenetic study of HCV strains using partial envelope gene sequences (E1-E2) of HCV genotype 6a strains from the suspected source patient, the environment, and the index patient were performed. RESULTS: Investigations and data review revealed no further cases of HCV genotype 6a infection in the transplant unit. However, a suspected source with a high HCV load was identified. HCV genotype 6a was found in a contaminated reusable blood-collection tube holder with barely visible blood and was identified as the only shared item posing risk of transmission to the index case patient. Also, 14 episodes of sequential blood collection from the source patient and the index case patient were noted on the computerized time log of the laboratory barcoding system during their 13 days of cohospitalization in the liver transplant ward. Disinfection of the tube holders was not performed after use between patients. Blood collection simulation experiments showed that HCV and technetium isotope contaminating the tip of the sleeve capping the sleeved-needle can reflux back from the vacuum-specimen tube side to the patient side. CONCLUSIONS: A reusable blood-collection tube holder without disinfection between patients can cause a nosocomial HCV infection. Single-use disposable tube holders should be used according to the recommendations by Occupational Safety and Health Administration and World Health Organization.

Radioembolization with 90Y glass microspheres for hepatocellular carcinoma: significance of pretreatment 11C-acetate and 18F-FDG PET/CT and posttreatment 90Y PET/CT in individualized dose prescription.

PURPOSE: The aim of this study was to establish an algorithm for the prescription of 90Y glass microsphere radioembolization (90Y-GMRE) of HCC in individual patients based on the relationship between tumour dose (TD) and response validated by 90Y PET/CT dosimetry and dual-tracer PET/CT metabolic parameters. METHODS: The study group comprised 62 HCC patients prospectively recruited for 90Y-GMRE who underwent pretreatment dual-tracer (11C-acetate and 18F-FDG) PET/CT as surrogate markers of HCC cellular differentiation. Pretreatment tumour-to-nontumour ratio on 99mTc-MAA SPECT/CT (T/NTMAA) was correlated with posttreatment 90Y PET/CT T/NT90Y after quantification validation. The TD-response relationship for HCC of different tracer groups was assessed on follow-up PET/CT 2 months after treatment. RESULTS: 90Y PET/CT was accurate in the measurement of recovery of injected 90Y activity (81.9-99.9%, median 94.8%). Pretreatment SPECT/CT T/NTMAA was strongly correlated with posttreatment 90Y PET/CT T/NT90Y (5.6 ± 3.2 versus 5.9 ± 3.5, T/NT90Y 1.01 × T/NTMAA + 0.161, r = 0.918, P < 0.05). The response rates were 72.4% (21/29), 70.6% (12/17) and 25% (4/16) for well, moderately and poorly differentiated HCC, respectively. The cut-off TD for a good response was significantly different between poorly differentiated and well/moderately differentiated HCC (262 Gy versus 152/174 Gy) with 89.2% sensitivity and 88% specificity. At a limiting tolerated liver dose of 70 Gy, the T/NTMAA thresholds for predicting a good response in poorly differentiated and well/moderately differentiated HCC were 3.5 and 2.0/2.3. Disregarding HCC cellular differentiation, the cut-off TD became 170 Gy, with lower sensitivity (70.3%) and specificity (76%). CONCLUSION: 90Y PET/CT can provide accurate dosimetry for 90Y-GMRE. Pretreatment T/NTMAA predicts posttreatment T/NT90Y. The TD thresholds for a good response are tracer-dependent, with a strong correlation between HCC radiosensitivity and cellular differentiation and other PET-based parameters. These cytokinetic factors improve treatment efficacy while minimizing organ damage for the prescription of personalized 90Y-GMRE.

68Ga-DOTATOC and 68Ga-PSMA PET/CT Unmasked a Case of Prostate Cancer With Neuroendocrine Differentiation.

A bedridden 90-year-old man with fever and elevated prostate-specific antigen (PSA) (49 ng/mL) was referred for differentiation between infection and tumor. F-FDG PET/CT was negative for infection, but Ga-PSMA PET/CT showed multiple lesions in prostate gland with infiltration to bladder wall and seminal vesicle, consistent with locally advanced prostate cancer. The lesion with the highest Ga-PSMA uptake was strongly avid for Ga-DOTATOC, suggesting neuroendocrine tumor differentiation. After hormonal therapy, PSA normalized, but chromogranin-A increased (from 251 to 398 ng/mL), inferring progression of neuroendocrine tumor differentiation. Advanced prostate cancer may require investigation for pathological neuroendocrine transformation, although PSA may suggest improvement.

Reduced striatal dopamine transmission in REM sleep behavior disorder comorbid with depression.

OBJECTIVE: To investigate dopamine transmission in patients with comorbid REM sleep behavior disorder (RBD) and major depressive disorder (MDD). METHODS: This is a case-control study including 11 medicated patients with comorbid RBD and MDD (mean age 47.5 ± 8.2), 8 medicated patients with MDD only (mean age 47.9 ± 8.4), and 10 healthy participants (mean age 46.5 ± 10.6 years). They underwent clinical assessment, video-polysomnography, olfactory tests, and neuroimaging studies ((18)F-DOPA, (11)C-raclopride, and (18)F-FDG PET neuroimaging). RESULTS: Compared with the 2 control groups, patients with comorbid RBD and MDD had significantly lower (18)F-DOPA uptake at 60 minutes in the putamen and caudate after controlling for age and sex effect (p < 0.05). There were no significant differences for the (11)C-raclopride and (18)F-FDG-PET. The (18)F-DOPA uptake in putamens had significant inverse correlation with severity of RBD symptoms (p < 0.01) and REM-related tonic muscle activity (p < 0.01). The comorbid RBD and MDD group had more impairment in olfactory function. CONCLUSION: Patients with comorbid RBD and MDD had presynaptic dopamine dysfunction and impaired olfactory function. There is a distinct possibility that the development of RBD symptoms among patients with MDD may represent an early phase of α-synucleinopathy neurodegeneration instead of a merely antidepressant-induced condition.

11C-acetate PET/CT for metabolic characterization of multiple myeloma: a comparative study with 18F-FDG PET/CT.

UNLABELLED: We prospectively compared (11)C-acetate with (18)F-FDG in a PET/CT evaluation of multiple myeloma (MM), specifically on diagnostic accuracy, identification of high-risk patients, and monitoring of treatment response. METHODS: Dual-tracer PET/CT was performed on 35 pathologically and clinically confirmed and untreated patients (26 with symptomatic MM, 5 with smoldering MM, and 4 with monoclonal gammopathy of unknown significance) and 20 individuals with normal marrow. RESULTS: (11)C-acetate showed significant incremental value over (18)F-FDG (84.6% vs. 57.7%) for positively identifying patients with diffuse and focal symptomatic MM, and was negative in patients with indolent smoldering MM and monoclonal gammopathy of unknown significance. Three functional parameters-number of (11)C-acetate-avid and (18)F-FDG-avid focal bone lesions and (11)C-acetate general marrow activity-strongly correlated with ß-2-microglobulin as surrogate imaging markers of tumor burden. After induction chemotherapy, the metabolic change in (11)C-acetate general marrow activity correlated with clinical response. CONCLUSION: Metabolic characterization of MM in diagnosis, risk stratification, and treatment monitoring can be done more accurately by assessing lipid metabolism with (11)C-acetate than by assessing glucose metabolism with (18)F-FDG.

(11)C-acetate PET/CT in a case of recurrent hemangiopericytoma.

Intracranial hemangiopericytoma (IHPC) is a rare tumor representing less than 1% of all CNS tumors and is often indistinguishable from meningioma on structural imaging alone. Unlike meningioma, IHPC is an aggressive tumor with the propensity for early locoregional recurrence and distant metastases. Hence, its management strategies differ greatly from that of meningioma. Some investigators have reported the potential role of multitracers (F-FDG, C-methionine, and O-H2O) PET imaging in distinguishing IHPC from meningioma. We described the findings of dual-tracer (C-acetate and F-FDG) PET/CT imaging in a histopathologically proven case of IHPC with extensive extracranial osseous metastases that showed significantly greater C-acetate avidity.

(11)C-acetate as a new biomarker for PET/CT in patients with multiple myeloma: initial staging and postinduction response assessment.

PURPOSE: We investigated the potential value of (11)C-acetate (ACT) PET/CT in characterizing multiple myeloma (MM) compared with (18)F-FDG PET/CT. Bone marrow histological and whole-body (WB) MRI findings served as the reference standards. METHODS: In this prospective study, 15 untreated MM patients (10 men and 5 women, age range 48-69 years) underwent dual-tracer (11)C-ACT and (18)F-FDG PET/CT and WB MRI for pretreatment staging, and 13 of them had repeated examinations after induction therapy. Diffuse and focal bone marrow uptake was assessed by visual and quantitative analyses, including measurement of the maximum standardized uptake value (SUVmax). Between-group differences and correlations were assessed with the Mann-Whitney U test and the Pearson test. RESULTS: At staging, all 15 patients had diffuse myeloma involvement upon bone marrow examination with 30-90 % of plasma cell infiltrates. Diffuse infiltration was detected in all of them (100 %) using (11)C-ACT with a positive correlation between bone marrow uptake values and percentages of plasma cell infiltrates (r = +0.63, p=0.01). In contrast, a diagnosis of diffuse infiltration could be established using (18)F-FDG in only six patients (40 %). Focal lesions were shown in 13 patients on both (11)C-ACT PET/CT and WB MRI, and in 10 patients on (18)F-FDG PET/CT. Focal lesions demonstrated (11)C-ACT uptake with a mean SUVmax of 11.4 ± 3.3 (range 4.6-19.6, n=59), which was significantly higher than the (18)F-FDG uptake (mean SUVmax 6.6 ± 3.1, range 2.3-13.7, n=29; p<0.0001). After treatment, the diffuse bone marrow (11)C-ACT uptake showed a mean SUVmax reduction of 66 % in patients with at least a very good partial response versus 34 % in those with at most a partial response only (p=0.01). CONCLUSION: PET/CT using (11)C-ACT as a biomarker showed a higher detection rate for both diffuse and focal myeloma lesions at diagnosis than using (18)F-FDG, and may be valuable for response assessment.