Faculty Bibliography

Purpose To assess the diagnostic performance of the callosal angle (CA) and Evans index (EI) measures and to determine their role versus automated volumetric methods in clinical radiology. Materials and Methods Magnetic resonance (MR) examinations performed before surgery (within 1-5 months of the MR examination) in 36 shunt-responsive patients with normal-pressure hydrocephalus (NPH; mean age, 75 years; age range, 58-87 years; 26 men, 10 women) and MR examinations of age- and sex-matched patients with Alzheimer disease (n = 34) and healthy control volunteers (n = 36) were studied. Three blinded observers independently measured EI and CA for each patient. Volumetric segmentation of global gray matter, white matter, ventricles, and hippocampi was performed by using software. These measures were tested by using multivariable logistic regression models to determine which combination of metrics is most accurate in diagnosis. Results The model that used CA and EI demonstrated 89.6%-93.4% accuracy and average area under the curve of 0.96 in differentiating patients with NPH from patients without NPH (ie, Alzheimer disease and healthy control). The regression model that used volumetric predictors of gray matter and white matter was 94.3% accurate. Conclusion CA and EI may serve as a screening tool to help the radiologist differentiate patients with NPH from patients without NPH, which would allow for designation of patients for further volumetric assessment. (c) RSNA, 2017.

As the optogenetic field expands, the need for precise targeting of neocortical circuits only grows more crucial. This work demonstrates a technique for using Solidworks^®computer-aided design (CAD) and readily available stereotactic brain atlases to create a three-dimensional (3-D) model of the dorsal region of area visual cortex 4 (V4D) of the macaque monkey (Macaca fascicularis) visual cortex. The 3-D CAD model of the brain was used to customize an [Formula: see text] Utah optrode array (UOA) after it was determined that a high-density ([Formula: see text]) UOA caused extensive damage to marmoset (Callithrix jacchus) primary visual cortex as assessed by electrophysiological recording of spiking activity through a 1.5-mm-diameter through glass via. The [Formula: see text] UOA was customized for optrode length ([Formula: see text]), optrode width ([Formula: see text]), optrode pitch ([Formula: see text]), backplane thickness ([Formula: see text]), and overall form factor ([Formula: see text]). Two [Formula: see text] UOAs were inserted into layer VI of macaque V4D cortices with minimal damage as assessed in fixed tissue cytochrome oxidase staining in nonrecoverable surgeries. Additionally, two [Formula: see text] arrays were implanted in mice (Mus musculus) motor cortices, providing early evidence for long-term tolerability (over 6 months), and for the ability to integrate the UOA with a Holobundle light delivery system toward patterned optogenetic stimulation of cortical networks.

Background: Urine chemistry is a determinant of stone formation in cystinuria. We previously showed that positive cystine capacity (CysCap), a measure of higher cystine solubility, led to fewer stone events. We queried the RKSC Cystinuria Registry to determine urinary and medication variables associated with positive (CysCap+), rather than negative (CysCap-) values.
Method(s): This is the 1st report from the Cystinuria Registry, with data on 300 people with cystinuria (142 males, 158 females; age at enrollment 38 +/- 17 years). 112 participants had 306 determinations of CysCap, measured by Litholink (Chicago, IL). In this cross-sectional study we compared variables associated with CysCap+ vs CysCap-.
Result(s): Lower urine Na (r=0.48; Fig 1A) and creatinine (r=0.62, not shown) were associated with lower 24h urine cystine (UC; P<0.001). Increasing CysCap values were seen with increasing urine pH (rs=0.45, Fig 1B), volume (rs=0.44) and decreasing UC (rs=-0.44 Fig 1C; all P<0.001). Dividing Cyscap determinations into CysCap+ and CysCapgroups (Table), only higher urine volume and greater daily citrate doses were different. Relatively few participants were taking citrate or tiopronin.
Conclusion(s): Higher urine pH and volume and lower UC were associated with less lithogenic urine; lower UC was seen with less Na and creatinine. Higher volume and citrate doses distinguished patients with less lithogenic urine. Many patients with cystinuria may be undertreated and would benefit from better dietary adherence. (Table Presented)

Background: Symptoms of psychosis, including hallucinations and delusions, are relatively frequent in Parkinson disease and Lewy body dementia, particularly in patients receiving levodopa and dopamin-ergic agonists. However, the prevalence of psychosis in multiple system atrophy (MSA) is unknown. We aimed to determine the prevalence and characteristics of psychotic symptoms in patients with MSA, and factors associated with their development. Methods: Consecutive patients with probable MSA without previous history of psychiatric disorders were prospectively enrolled in a longitudinal observational study. The presence of hallucinations and delusions was determined during a standardized clinical interview and quantified with the Scale for the Assessment of Positive Symptoms in Parkinson disease (SAPS-PD). Patients also underwent full evaluation of visual acuity, cognition (Montreal Cognitive Assessment, MoCA), motor function and disease severity [United Multiple System Atrophy Rating Scale (UMSARS)]. Results: Of the 31 consecutive patients with probable MSA (17 men; mean age 64 +/- 8 years; 13 MSA-P and 14 MSA-C), 6 (19%) had positive symptoms of psychosis including delusions and/or hallucinations. All but one patient had the cerebellar phenotype of the disease (MSA-C). Auditory hallucinations occurred in 4 patients, visual hallucinations in 4, persecutory delusions in 3, and jealousy delusions in 3. No patients reported somatic or tactile hallucinations. Psychosis symptoms were extremely severe and refractory to treatment in 2 cases with MSA-C, both of whom died within 12 months of psychosis onset. Psychotic symptoms were not associated with levodopa or other antiparkinsonian medication treatment, visual acuity, cognitive score, depression score, or duration of illness. Conclusions: Psychotic symptoms occur in *20% of patients with MSA, the vast majority of whom have MSA-C. Severe refractory psychotic symptoms appear to be associated with poor prognosis (death < 1 year). Our results suggest that psychotic symptoms in MSA are unrelated to visual system abnormalities

Introduction: Familial dysautonomia (FD) is a rare autosomal recessive disorder caused by a point mutation in the IKBKAP gene, resulting in reduction of the IkappaB Kinase-associated protein/Elongator protein 1 (IKAP/ELP1). ELP1 is a transcriptional regulator that targets downstream genes involved with cell migration, stability and survival. We hypothesized that ELP1-associated abnormalities may increase the incidence and prevalence of neoplasia and cancer in FD. Methods: Retrospective chart review of the New York University FD Patient International Registry, which contains standardized clinical information on patients with genetically confirmed FD since 1970. We identified cases with neoplasia or cancer, and reviewed their demographics, tumor type and age at diagnosis. Results: At the time of writing, of the 674 patients with FD reviewed, we identified 25 cases of neoplasia, which included 12 cases of cancer. The prevalence of neoplasia in the FD population was 3.7% and the prevalence of cancer was 1.8%. Average age at cancer diagnosis was 29 years, significantly younger than in the general population (66 years). Additionally, 16% of all neoplasia were tumors derived from neural crest cells. There was no association between growth hormone treatment and the prevalence of neoplasia or cancer. Conclusions: Patients with FD have higher rates of neoplasia and cancer than previously reported in the literature. Overall, the FD population develops cancer and tumors at a much younger atypical age than the general population. Our results suggest that ELP1 plays an important role in tumor genesis and may explain the high prevalence of neoplasia and cancer in patients with FD

OBJECTIVES: The aim of this study was to assess the applicability of Dixon radial volumetric encoding (Dixon-RAVE) for comprehensive dynamic contrast-enhanced 3D magnetic resonance imaging (MRI) of the breast using a combination of radial sampling, model-based fat/water separation, compressed sensing, and parallel imaging. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, 24 consecutive patients underwent bilateral breast MRI, including both conventional fat-suppressed and non-fat-suppressed precontrast T1-weighted volumetric interpolated breath-hold examination (VIBE). Afterward, 1 continuous Dixon-RAVE scan was performed with the proposed approach while the contrast agent was injected. This scan was immediately followed by the acquisition of 4 conventional fat-saturated VIBE scans. From the comprehensive Dixon-RAVE data set, different image contrasts were reconstructed that are comparable to the separate conventional VIBE scans.Two radiologists independently rated image quality, conspicuity of fibroglandular tissue from fat (FG), and degree of fat suppression (FS) on a 5-point Likert-type scale for the following 3 comparisons: precontrast fat-suppressed (pre-FS), precontrast non-fat-suppressed (pre-NFS), and dynamic fat-suppressed (dyn-FS) images. RESULTS: When scores were averaged over readers, Dixon-RAVE achieved significantly higher (P < 0.001) degree of fat suppression compared with VIBE, for both pre-FS (4.25 vs 3.67) and dyn-FS (4.10 vs 3.46) images. Although Dixon-RAVE had lower image quality score compared with VIBE for the pre-FS (3.56 vs 3.67, P = 0.490), the pre-NFS (3.54 vs 3.88, P = 0.009), and the dyn-FS images (3.06 vs 3.67, P < 0.001), acceptable or better diagnostic quality was achieved (score >/= 3). The FG score for Dixon-RAVE in comparison to VIBE was significantly higher for the pre-FS image (4.23 vs 3.85, P = 0.044), lower for the pre-NFS image (3.98 vs 4.25, P = 0.054), and higher for the dynamic fat-suppressed image (3.90 vs 3.85, P = 0.845). CONCLUSIONS: Dixon-RAVE can serve as a one-stop-shop approach for comprehensive T1-weighted breast MRI with diagnostic image quality, high spatiotemporal resolution, reduced overall scan time, and improved fat suppression compared with conventional imaging.

Objectives: Temper outbursts are frequently considered symptoms of irritability within the context of ODD, mood disorder, and anxiety disorder. However, even when chronic irritability is not present, they are associated with significant functional impairments. We will provide an overview of our research program that takes a multimodal approach to understanding severe temper outbursts in young children. Methods: We evaluated 216 boys and girls (ages 5-9 years; 73% boys) from diverse socioeconomic backgrounds who comprised three groups: 1) children with severe temper outbursts (STO; n = 80); 2) children with ADHD without outbursts (ADHD; n = 79); and 3) typically developing children (TDC; n = 57). Severe temper outbursts were defined as follows: 1) occurring at least three times per week; 2) lasting >10 minutes; 3) excessive for developmental level; and 4) causing significant impairment. Parents completed a semistructured diagnostic interview about their child and questionnaires about their child's behavior and emotion regulation skills. Children completed brief IQ and language screeners, questionnaires about their emotions and behavior, and tasks assessing frustration tolerance and emotion regulation. A number of these children (64 percent) successfully completed an MRI session that included resting-state, structural, and diffusion tension imaging scans. Results: Approximately 84 percent of the STO group received an ADHD diagnosis, 67 percent were diagnosed with ODD, 28 percent were diagnosed with an anxiety disorder, and 12 percent were diagnosed with a mood disorder. Few exhibited chronic irritabilities based on parent report. On an emotion regulation task, the STO group demonstrated deficits in regulating negative affect in response to frustration. Findings from the resting-state fMRI analyses suggest disruptions in dorsal anterior cingulate cortex (dACC) circuitry associated with tantrum severity. Tantrum severity was also related to cortical thickness of the dACC. Conclusions: Children with severe temper outbursts represent a highly impaired group, even when chronic irritability is not present. Evidence suggests an association between these outbursts and disruptions in dACC circuitry, a region implicated in the expression and regulation of frustration. Such findings have important implications for future conceptualization and treatment of young children with severe temper outbursts

APOE4 is the strongest genetic risk factor for late-onset Alzheimer disease. ApoE4 increases brain amyloid-beta pathology relative to other ApoE isoforms. However, whether APOE independently influences tau pathology, the other major proteinopathy of Alzheimer disease and other tauopathies, or tau-mediated neurodegeneration, is not clear. By generating P301S tau transgenic mice on either a human ApoE knock-in (KI) or ApoE knockout (KO) background, here we show that P301S/E4 mice have significantly higher tau levels in the brain and a greater extent of somatodendritic tau redistribution by three months of age compared with P301S/E2, P301S/E3, and P301S/EKO mice. By nine months of age, P301S mice with different ApoE genotypes display distinct phosphorylated tau protein (p-tau) staining patterns. P301S/E4 mice develop markedly more brain atrophy and neuroinflammation than P301S/E2 and P301S/E3 mice, whereas P301S/EKO mice are largely protected from these changes. In vitro, E4-expressing microglia exhibit higher innate immune reactivity after lipopolysaccharide treatment. Co-culturing P301S tau-expressing neurons with E4-expressing mixed glia results in a significantly higher level of tumour-necrosis factor-alpha (TNF-alpha) secretion and markedly reduced neuronal viability compared with neuron/E2 and neuron/E3 co-cultures. Neurons co-cultured with EKO glia showed the greatest viability with the lowest level of secreted TNF-alpha. Treatment of P301S neurons with recombinant ApoE (E2, E3, E4) also leads to some neuronal damage and death compared with the absence of ApoE, with ApoE4 exacerbating the effect. In individuals with a sporadic primary tauopathy, the presence of an epsilon4 allele is associated with more severe regional neurodegeneration. In individuals who are positive for amyloid-beta pathology with symptomatic Alzheimer disease who usually have tau pathology, epsilon4-carriers demonstrate greater rates of disease progression. Our results demonstrate that ApoE affects tau pathogenesis, neuroinflammation, and tau-mediated neurodegeneration independently of amyloid-beta pathology. ApoE4 exerts a 'toxic' gain of function whereas the absence of ApoE is protective.

Long-term modifications of neuronal connections are critical for reliable memory storage in the brain. However, their locus of expression-pre- or postsynaptic-is highly variable. Here we introduce a theoretical framework in which long-term plasticity performs an optimization of the postsynaptic response statistics toward a given mean with minimal variance. Consequently, the state of the synapse at the time of plasticity induction determines the ratio of pre- and postsynaptic modifications. Our theory explains the experimentally observed expression loci of the hippocampal and neocortical synaptic potentiation studies we examined. Moreover, the theory predicts presynaptic expression of long-term depression, consistent with experimental observations. At inhibitory synapses, the theory suggests a statistically efficient excitatory-inhibitory balance in which changes in inhibitory postsynaptic response statistics specifically target the mean excitation. Our results provide a unifying theory for understanding the expression mechanisms and functions of long-term synaptic transmission plasticity.

The dragonbloodins are a pair of complex flavonoid trimers that have been isolated from the palm tree Daemonorops draco, one of the sources of the ancient resin known as "dragon's blood". We present a short synthesis that clarifies their relative configurations and sheds light on their origin in Nature. This synthesis features biomimetic cascade reactions that involve both ionic and radical intermediates. The biogenetic relationships between dracorhodin, the dracoflavans C, and the dragonbloodins A1 and A2 are discussed.