Arterial spin labeling demonstrates preserved regional cerebral blood flow in the P301L mouse model of tauopathy

There is growing evidence for the vascular contribution to cognitive impairment and dementia in Alzheimer’s disease (AD) and other neurodegenerative diseases. While perfusion deficits have been observed in patients with Alzheimer’s disease and tauopaties, little is known about the role of tau in vascular dysfunction. In the present study, regional cerebral blood (rCBF) was characterized in P301L mice with arterial spin labeling. No differences in rCBF in P301L mice compared to their age-matched non-transgenic littermates at mid (10–12 months of age) and advanced (19–21 months of age) disease stages. This was concomitant with preservation of cortical brain structure as assessed with structural T2-weighted magnetic resonance imaging. These results show that hypoperfusion and neurodegeneration are not a phenotype of P301L mice. More studies are thus needed to understand the relationship of tau, neurodegeneration and vascular dysfunction and its modulators in AD and primary tauopathies.

Reduced Regional Cerebral Blood Flow Measured by 99mTc-Hexamethyl Propylene Amine Oxime Single-Photon Emission Computed Tomography in Microgravity Simulated by 5-Day Dry Immersion

Microgravity induces a cephalad fluid shift that is responsible for cephalic venous stasis that may increase intracranial pressure (ICP) in astronauts. However, the effects of microgravity on regional cerebral blood flow (rCBF) are not known. We therefore investigated changes in rCBF in a 5-day dry immersion (DI) model. Moreover, we tested thigh cuffs as a countermeasure to prevent potential microgravity-induced modifications in rCBF. Around 18 healthy male participants underwent 5-day DI with or without a thigh cuffs countermeasure. They were randomly allocated to a control (n=9) or cuffs (n=9) group. rCBF was measured 4days before DI and at the end of the fifth day of DI (DI5), using single-photon emission computed tomography (SPECT) with radiopharmaceutical 99mTc-hexamethyl propylene amine oxime (99mTc-HMPAO). SPECT images were processed using statistical parametric mapping (SPM12) software. At DI5, we observed a significant decrease in rCBF in 32 cortical and subcortical regions, with greater hypoperfusion in basal ganglia (right putamen peak level: z=4.71, puncorr<0.001), bilateral occipital regions (left superior occipital peak level: z=4.51, puncorr<0.001), bilateral insula (right insula peak level: 4.10, puncorr<0.001), and bilateral inferior temporal (right inferior temporal peak level: 4.07, puncorr<0.001). No significant difference was found between the control and cuffs groups on change in rCBF after 5days of DI. After a 5-day DI, we found a decrease in rCBF in cortical and subcortical regions. However, thigh cuffs countermeasure failed to prevent hypoperfusion. To date, this is the first study measuring rCBF in DI. Further investigations are needed in order to better understand the underlying mechanisms in cerebral blood flow (CBF) changes after exposure to microgravity.

Connectivity and Patterns of Regional Cerebral Blood Flow, Cerebral Glu- cose Uptake, and Aβ-Amyloid Deposition in Alzheimer's Disease (Early and Late-Onset) Compared to Normal Ageing

Purpose: The aim of this study was to investigate the differences in early (EOAD) and late (LOAD) onset of Alzheimer ́s disease, as well as glucose uptake, regional cerebral blood flow (R1), amyloid depositions, and functional brain connectivity between normal young (YC) and Old Controls (OC). Methodology: The study included 22 YC (37 ± 5 y), 22 OC (73 ± 5.9 y), 18 patients with EOAD (63 ± 9.5 y), and 18 with LOAD (70.6 ± 7.1 y). Patients underwent FDG and PIB PET/CT. R1 im- ages were obtained from the compartmental analysis of the dynamic PIB acquisitions. Images were analyzed by a voxel-wise and a VOI-based approach. Functional connectivity was studied from the R1 and glucose uptake images. Results: OC had a significant reduction of R1 and glucose uptake compared to YC, predominantly at the dorsolateral and mesial frontal cortex. EOAD and LOAD vs. OC showed a decreased R1 and glucose uptake at the posterior parietal cortex, precuneus, and posterior cingulum. EOAD vs. LOAD showed a reduction in glucose uptake and R1 at the occipital and parietal cortex and an in- creased at the mesial frontal and temporal cortex. There was a mild increase in an amyloid deposi- tion at the frontal cortex in LOAD vs. EOAD. YC presented higher connectivity than OC in R1 but lower connectivity considering glucose uptake. Moreover, EOAD and LOAD showed a decreased connectivity compared to controls that were more pronounced in glucose uptake than R1. Conclusion: Our results demonstrated differences in amyloid deposition and functional imaging be- tween groups and a differential pattern of functional connectivity in R1 and glucose uptake in each clinical condition. These findings provide new insights into the pathophysiological processes of AD and may have an impact on patient diagnostic evaluation.

Regional Cerebral Blood Flow Abnormalities in Neurosyphilis: A Pilot SPECT Study

Objective: Clinical and radiological findings on neurosyphilis are fairly non-specific and there is a paucity of functional neuroimaging studies on neurosyphilis other than case reports and case series. The purpose of this study was to investigate brain perfusion abnormalities in patients with neurosyphilis.Methods: Four HIV-negative neurosyphilis patients and 4 healthy controls underwent clinical evaluation, brain technetium-99m ethyl cysteinate dimer (99mTc-ECD) single-photon emission computed tomography (SPECT) imaging, and neuropsychological assessments which included the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Clinical Dementia Rating—Sum of Boxes (CDR-SOB), and Global Deterioration Scale (GDS). Voxel-wise differences in regional cerebral blood flow were compared between the two groups.Results: Neuropsychological test results indicated cognitive impairment in all patients. SPECT analysis revealed multifocal hypoperfusion predominantly in the frontal, insular, and posterior cingulate regions in neurosyphilis patients compared with healthy controls (family-wise error corrected p < 0.05).Conclusions: Together with previous findings, our results suggest that the hypoperfusion in the frontal, insular, and posterior cingulate regions may reflect cognitive impairments observed in neurosyphilis patients. Further studies with larger samples are needed to confirm our findings.

Case Report: Changes in Regional Cerebral Blood Flow in Chronic Akathisia of a Depressed Patient Before and After Electroconvulsive Therapy Treatment

Akathisia, which characterized by subjective restlessness and objective hyperactivity, is induced mostly by antipsychotics and antidepressants. Chronic akathisia is defined as persistence of symptoms for more than 3 months. The pathophysiology of chronic akathisia remains unclear. This report describes a depressed patient, a 66-year-old woman with a diagnosis of major depressive disorder, with chronic akathisia. Her regional cerebral blood flow (rCBF) was measured using single photon emission computed tomography (SPECT) before and after the treatment with electroconvulsive therapy (ECT). She had experienced akathisia-like symptoms three times prior because of risperidone, escitalopram, and clomipramine administration, accompanied by major depression. After levomepromazine was added to quetiapine to treat insomnia, she developed akathisia symptoms such as a sense of restlessness and inability to sit in one place for a few minutes. These antipsychotics were withdrawn. Propranolol was administered, leading to no apparent improvement for 8 months. After she was diagnosed as having major depressive disorder and chronic akathisia, she received 10 sessions of bilateral ECT. Her depressive symptoms improved greatly. Akathisia disappeared completely after ECT. SPECT revealed that rCBF was decreased in the middle frontal gyrus and parietal lobe, that it was increased in the thalamus, fusiform gyrus, and cerebellum before ECT, and that these abnormalities in rCBF were approaching normal levels after ECT. Findings presented in this report suggest ECT as a beneficial treatment for chronic akathisia. Altered rCBF in the middle frontal gyrus, parietal lobe, thalamus, fusiform gyrus, and cerebellum, and especially decreased rCBF in the parietal lobe, may be related to the pathophysiology of chronic akathisia.

A-67 Measuring Regional Cerebral Blood Flow with Single-Photon Emission Computed Tomography (SPECT) in Obsessive–Compulsive Disorder

Objective To identify regional cerebral blood flow (rCBF) differences between individuals with Obsessive–Compulsive Disorder (OCD) and healthy controls. Mehtods: Healthy controls (n = 81, Mage = 41.9, 53.0% female, 42.0% Caucasian) and persons diagnosed by psychiatric examination with OCD (n = 1020, Mage = 34.8, 33.6% female, 66.3% Caucasian) were selected from a deidentified adult clinical outpatient database. Those with comorbid diagnoses were included. Significant differences (alpha = 0.001) were found for age [t(1099) = −4.4], gender [χ2(2) = 25.7], and race [χ2(12) = 30.1] between groups and therefore were controlled for. Significant rCBF differences were noted in the cerebellum [left:F(1,1096) = 21.6; right:F(1,1096) = 18.3], limbic system [left:F(1,1096) = 12.2; right:F(1,1096) = 10.4], and basal ganglia [left:F(1,1096) = 18.6; right:F(1,1096) = 18.3]. Results Group means comparisons indicated higher perfusion in the cerebellum for the OCD group. Lower perfusion was found in the limbic system and basal ganglia in the OCD group. This study found higher perfusion in the cerebellum among the OCD group. Previous research found increased rCBF in the left cerebellum in OCD before pharmacotherapy. In the right cerebellum, increased rCBF was found among participants with early-onset OCD. Conclusion Overall, there is limited research on the cerebellum because of its use as a reference point. No research was found regarding the limbic system in OCD using SPECT; however, other neuroimaging found increased amygdala reactivity to emotional face stimuli. This study found lower perfusion in the basal ganglia among the OCD group. Previous research found hypoperfusion in the right; however, hypoperfusion in the left was not significant. Updated OCD and rCBF research with SPECT are needed. Limitations included the inclusion of comorbidities and use of DSM-IV-TR rather than DSM-5 diagnosis criteria.