Clinical Correlates of the PET-based Braak Staging Framework in Alzheimer's Disease.

In vivo Alzheimer's disease diagnosis and staging is traditionally based on clinical features. However, the agreement between clinical and pathological Alzheimer's disease diagnosis, whose diagnosis assessment includes amyloid and Braak histopathological tau staging, is not completely convergent. The development of positron emission tomography (PET) tracers targeting neurofibrillary tangles offers prospects for advancing the staging of Alzheimer's disease from both biological and clinical perspectives. Recent advances in radiochemistry made it possible to apply the postmortem Braak staging framework to tau-PET images obtained in vivo. Here, our aim is to provide a narrative review of the current literature on the relationship between Alzheimer's disease clinical features and the PET-based Braak staging framework. Overall, the available studies support the stepwise increase in disease severity following the advance of PET-based Braak stages, with later stages being associated with worse cognitive and clinical symptoms. In line with this, there is a trend for unimpaired cognition, mild cognitive impairment, and Alzheimer's disease dementia to be compatible with early, intermediate, and late patterns of tau deposition based on PET-based Braak stages. Moreover, neuropsychiatric symptom severity seems to be linked to the extent of tau-PET signal across Braak areas. In sum, this framework seems to correspond well with the clinical progression of Alzheimer's disease, which is an indication of its potential utility in research and clinical practice, especially for detecting preclinical tau levels in individuals without symptoms. However, further research is needed to improve the generalizability of these findings and to better understand the applications of this staging framework.

The association of postnatal urinary tract dilation risk score with clinical outcomes.

BACKGROUND: There are limited data on the predictive value of the consensus urinary tract dilation (UTD) score with respect to subsequent clinical diagnoses. We sought to define the relationship between postnatal UTD risk score and clinical outcomes during childhood. METHODS: Complete ultrasound image sets from a random selection of infants aged 0-90 days undergoing initial ultrasound at a single institution for prenatal hydronephrosis between 2012 and 2014 were assigned a UTD score by 1 pediatric urologist and 1 pediatric radiologist. Urinary tract dilation risk score was analyzed for association with a composite outcome comprising urinary tract infection, vesicoureteral reflux (VUR), ureteropelvic junction obstruction, non-refluxing megaureter (NRM), ureterocele, bladder outlet obstruction (BOO), and chronic kidney disease. Surgical intervention and resolution of UTD were evaluated separately. Descriptive and survival analyses were performed. RESULTS: Urinary tract dilation scores for 494 subjects were P0 in 23.5%, P1 in 26.5%, P2 in 23.5%, and P3 in 26.5%. Seventy-four percent were male. Median age at initial imaging was 28 days; median follow-up was 19.8 months. The composite outcome occurred in 138 of 494 patients (27.9%) and varied significantly (p < 0.001) by UTD score: 11.2% for P0, 10.7% for P1, 29.3% for P2, and 58.8% for P3. On survival analysis (Summary Figure), higher UTD grade was significantly associated with the composite outcome (hazard ratio for P3 vs. P0 was 7.4 [95% CI: 3.44-15.92, p < 0.001]). Urinary tract infection and VUR diagnosis varied by UTD score (p = 0.03 and p < 0.001, respectively). Ureteropelvic junction obstruction was diagnosed (based on MAG3 results) in 6.3% of patients, 84% of whom were P3. Non-refluxing megaureter was diagnosed in 7.7%. Ureterocele and BOO were uncommon (1.4%, and 0.6%, respectively). Surgical intervention was also associated with UTD risk, with 46% of P3 undergoing surgery vs. 1% of P0, 1% of P1, and 6% of P2 (p < 0.001). Resolution of UTD occurred in 41% (median 10.1 months) and varied significantly by UTD risk (p < 0.001). DISCUSSION: Urinary tract dilation risk score is associated with clinical events, although ascertainment bias may influence some of the differences in outcomes, particularly for VUR, because VCUG utilization varied by the UTD group. The lack of any significant difference in outcomes between patients with UTD P0 versus P1 suggests that the P1 category could be eliminated as it does not meaningfully distinguish between outcome risk. CONCLUSIONS: Higher UTD risk scores are strongly associated with genitourinary diagnoses during the first two years of life.

Preclinical molecular imaging of glutamatergic and dopaminergic neuroreceptor kinetics in obsessive compulsive disorder.

BACKGROUND: Molecular neuroimaging was applied in the quinpirole rat model for compulsive checking in OCD to visualize the D2- and mGluR5-receptor occupancy with Raclopride and ABP-688 microPET/CT. METHODS: Animals (n=48) were exposed to either saline (CTRL; 1mL/kg) or quinpirole (QP; dopamine D2-agonist, 0.5mg/kg) in a single injection (RAC and ABP acute groups) or twice-weekly during 7weeks (chronic group). Animals underwent PET/CT after the 1st injection (acute) or before initial exposure and following the 10th injection in week 5 (chronic). For the latter, each injection was paired with an open field test and video tracking. RESULTS: The QP animals displayed a strong increase in visiting frequency (checking) in the chronic group (+699.29%) compared to the control animals. Acute administration of the drug caused significant (p<0.01) decreases in D2R occupancy in the CP (-42.03%±4.01%). Chronical exposure resulted in significantly stronger decreases in the CP (-52.29%±3.79%). Furthermore significant increases in mGluR5 occupancy were found in the CP (10.36%±4.09%), anterior cingulate cortex (13.26%±4.01%), amygdala (24.36%±6.86%), entorhinal cortex (18.49%±5.14%) and nucleus accumbens (13.8%±4.87%) of the chronic group, not present after acute exposure. CONCLUSIONS: Compared to acute exposure, sensitisation to QP as a model for OCD differs both on a dopaminergic and glutamateric level, indicating involvement of processes such as receptor internalization and changes in extracellular availability of both neurotransmitters.

Radiologist performance in the interpretation of contrast enemas performed for Hirschsprung's disease in children >1 year of age.

AIM: To evaluate the diagnostic performance of contrast enemas (CEs) for the diagnosis of Hirschsprung's disease (HD). METHODS AND MATERIALS: CE studies performed as part of an HD workup in patients 1-18 years of age over a 10-year period were identified. All abnormal CE studies and an equal number of age-matched controls were included in the final study group. Two radiologists independently and blindly reviewed all CE studies for quality (scale of 0-3) and the presence of large colon calibre, colon redundancy, transition zone, rectosigmoid ratio, and abnormal contractions. Readers also determined whether a rectal biopsy would be recommended to confirm an HD diagnosis. Discrepancies were resolved in consensus. Findings were correlated with surgery and biopsy data. RESULTS: Out of 834 CE studies, 38 abnormal CE studies were identified (mean age 5.9 years) and included 38 matched controls. Seventeen of 76 patients were recommended for rectal biopsy, of which five were confirmed to have HD. Twelve of 70 (17.1%) were false positives, and were clinically confirmed not to have HD. The proportion of HD in the present population was 6/834 (0.72%). Of the 17 recommended for biopsy, CE studies showed 17/17 (100%) with an abnormal rectosigmoid ratio, 16/17 (94.1%) with redundant colon, and 15/17 (88%) with large colon. Of patients not recommended for biopsy, one was diagnosed with HD, (false negative, 16.7%). The diagnostic performance of CE was 83.3% sensitivity and 82.9% specificity. CONCLUSION: Few children >1 year of age were found to have HD and the diagnostic performance of the CE is moderately high. The CE examination is a valuable non-invasive imaging study to help exclude older children who may not have HD, thereby obviating the need for invasive rectal biopsy and surgery.

Comparison of [123I]MIBG and [131I]MIBG for imaging of neuroblastoma and other neural crest tumors.

Meta-iodobenzylguanidine (MIBG), an analog of the adrenergic neurotransmitter norepinephrine, has proven a valuable imaging agent for neuroendocrine and neural crest tumors. Over the past 3 decades, MIBG labeled with [131I] or [123I] has been used widely in imaging of neuroblastoma and pheochromocytoma. Before September 2008 [131I]MIBG was approved as a diagnostic agent only in the US. Due to the excellent physical characteristics of [123I] for imaging with modern scintillation cameras, [123I]MIBG is theoretically more suitable than [131I]MIBG in detecting tumors. In practice, use of [123I]MIBG or [131I]MIBG for diagnostic studies depends on availability and local preference. This review compares [123I]MIBG with [131I]MIBG in imaging of neuroblastoma and other neural crest tumors and also the physical properties of relevant radioisotopes. Dosimetry and scanning protocols of [123I]MIBG and [131I]MIBG, along with their value in depicting disease extent, assessing treatment response and predicting survival are also compared. The performance of post-therapy high-activity [131I]MIBG scans in lesion detectability is also addressed.

Treated unicameral bone cysts.

Unicameral bone cysts (UBCs) are a common benign entity involving the metaphysis of growing bone, occurring within the first two decades of life. Assessment of these lesions, both before and after surgery, is performed routinely utilizing radiographs. We present a review of UBCs at various stages of treatment, including both successful and incomplete healing, and describe the imaging findings throughout their postoperative course.

Activation of a muscle-specific enhancer by the Ski proto-oncogene.

In transgenic mice, muscle-specific expression of the c-ski oncogene induces hypertrophy exclusively in a subset of fast muscle fibers. Here we report that regulatory elements from two genes expressed in fast fibers, myosin light chain 1/3 (MLC) and muscle creatine kinase (MCK), were activated when co-transfected with c-ski expression vectors in myoblasts. The expression from the MLC enhancer was reduced when the c-ski oncogene was cotransfected with MyoD into NIH3T3 fibroblasts. Activation of the MLC enhancer by Ski also occurred in vivo, since bigenic progeny generated by mating MLC-CAT and MSV-skitransgenic mice displayed higher CAT activity in their muscles than did the MLC-CAT parental line. Identification of gene targets for the fiber-specific action of the c-ski gene product provides a molecular model that could be used for the further dissection of Ski-induced hypertrophy, both in tissue culture and in vivo.