Quantitative SPECT leads to improved performance in discrimination tasks related to prodromal Alzheimer's disease.

We investigated the impact of the quantitation and reconstruction protocol on clinical tasks. The performance of standard clinical reconstruction procedures in discrimination tasks related to the diagnosis of prodromal Alzheimer's disease (AD) was compared with the performance of a quantitative approach incorporating improved corrections for scatter, attenuation, intrinsic spatial resolution, and distance-dependent spatial resolution. METHODS: Seventeen normal controls (normal group), 56 subjects who did not have dementia, who did have memory problems, but who did not develop AD within 5 y of follow-up (questionable group), and 27 subjects who did not have dementia, who did have memory problems, and who did develop AD over the follow-up period (converter group) were considered in this study. (99m)Tc-hexamethylpropyleneamine oxime SPECT and MRI studies were performed for each subject at baseline. The standard quantitation protocol (STD), routinely used in our clinic, consisted of Compton window scatter correction followed by filtered backprojection with attenuation correction using a uniform attenuation map. In the improved quantitative approach (QUAN), projections were corrected for scatter by use of a general spectral method and reconstructed by use of ordered-subset(s) expectation maximization, incorporating corrections for collimator response and attenuation using both a uniform attenuation map (QUANunif) and a nonuniform attenuation map (QUANnonunif). Mean SPECT activity concentration and MRI volume were estimated for 7 structures: rostral anterior cingulate gyrus, caudal anterior cingulate gyrus, posterior cingulate gyrus, hippocampus, basal forebrain, amygdala, and the banks of the superior temporal sulcus. Data were analyzed by pairwise discriminant analysis, and performance in binary group discrimination was measured by correlated receiver-operating-characteristic analysis. RESULTS: The use of QUANnonunif yielded a small but systematic improvement in discrimination accuracy for normal versus converter groups (accuracy or area under the receiver-operating-characteristic curve [Az], 0.965), normal versus questionable groups (Az, 0.973), and questionable versus converter groups (Az, 0.881) compared with the results obtained with QUANunif (Az, 0.955, 0.962, and 0.866, respectively). Discrimination performance was significantly lower (P < 0.05) with STD than with QUAN in all 3 tasks (Az with STD, 0.906, 0.878, and 0.768, respectively). MRI volume estimation led to a lower overall performance in all 3 tasks than did QUANnonunif (Az with MRI, 0.947, 0.917, and 0.872, respectively). CONCLUSION: Improved quantitative image reconstruction with accurate compensation for scatter, attenuation, and variable collimator response led to significantly better performance in discrimination tasks related to the diagnosis of prodromal AD than did standard clinical reconstruction procedures. The use of a nonuniform brain attenuation map yields a small improvement in discrimination accuracy.     

Optimization of Ga-67 imaging for detection and estimation tasks: dependence of imaging performance on spectral acquisition parameters

We have compared the use of two (93 and 185 keV) and three (93, 185, and 300 keV) photopeaks for Ga-67 tumor imaging and optimized the placement of each energy window. METHODS: The bases for optimization and evaluation were ideal and Bayesian signal-to-noise ratios (SNR) for the detection of spheres embedded in a realistic anthropomorphic digital torso phantom and ideal SNR for the estimation of their size and activity concentration. Seven spheres of radii ranging from 1 to 3 cm, located at several sites in the torso, were simulated using a realistic Monte Carlo program. We also calculated the ideal SNR for the detection from simple phantom acquisitions. RESULTS: For detection and estimation tasks, the optimum windows were identical for all sphere sizes and locations. For the 93 keV photopeak, the optimal window was 84-102 keV for the detection and 87-102 keV for estimation; these windows are narrower than the 20% window often used in the clinic (83-101 keV). For the 185 keV photopeak, the optimal window was 170-220 keV for the detection and 170-215 keV for estimation; these are substantially different than the 15% window used in our clinic (171-199 keV). For the 300 keV photopeak, the optimal window for detection was 270-320 keV, and for estimation, 280-320 keV. Using the three optimized, rather than only the two lower-energy, windows yielded a 9% increase in the SNR for the detection of the 3 cm diam sphere (a 12% increase for a 2 cm diam sphere) and a 7% increase in the SNR for estimation of its size. For the acquired phantom data, detection also increased by 9%-12% when using three, rather than two, energy windows.     

Latency characteristics in specific pathogen-free chickens 21 and 35 days after intra-tracheal inoculation with vaccine or field strains of infectious laryngotracheitis virus

ABSTRACT

Latency is an important feature of infectious laryngotracheitis virus (ILTV) yet is poorly understood. This study aimed to compare latency characteristics of vaccine (SA2) and field (CL9) strains of ILTV, establish an in vitro reactivation system and examine ILTV infection in peripheral blood mononuclear cells (PBMC) in specific pathogen-free chickens. Birds were inoculated with SA2 or CL9 ILTV and then bled and culled at 21 or 35 days post-inoculation (dpi). Swabs (conjunctiva, palatine cleft, trachea) and trigeminal ganglia (TG) were examined for ILTV DNA using PCR. Half of the TG, trachea and PBMC were co-cultivated with cell monolayers to assess in vitro reactivation of ILTV infection. ILTV DNA was detected in the trachea of approximately 50% of ILTV‐inoculated birds at both timepoints. At 21?dpi, ILTV was detected in the TG only in 29% and 17% of CL9- and SA2-infected birds, respectively. At 35?dpi, ILTV was detected in the TG only in 30% and 10% of CL9- and SA2-infected birds, respectively. Tracheal organ co-cultures from 30% and 70% of CL9- and SA2-infected birds, respectively, were negative for ILTV DNA at cull but yielded quantifiable DNA within 6 days post-explant (dpe). TG co-cultivation from 30% and 40% of CL9-and SA2-infected birds, respectively, had detectable ILTV DNA within 6 dpe. Latency characteristics did not substantially vary based on the strain of virus inoculated or between sampling timepoints. These results advance our understanding of ILTV latency and reactivation.

RESEARCH HIGHLIGHTS

• Following inoculation, latent ILTV infection was detected in a large proportion of chickens, irrespective of whether a field or vaccine strain was inoculated.

• In vitro reactivation of latent ILTV was readily detected in tracheal and trigeminal ganglia co-cultures using PCR.

• ILTV latency observed in SPF chickens at 21 days post-infection was not substantially different to 35 days post-infection.

     

Diagnosis of Celiac Artery In‐Stent Thrombosis by Transesophageal Echocardiography

We present a case of a 70‐year‐old woman with severe peripheral arterial disease presenting with celiac artery in‐stent thrombosis diagnosed by transesophageal echocardiography (TEE). Routine assessment of the visceral arteries is not performed in most TEE studies. A review of the literature shows that the celiac and superior mesenteric arteries can be successfully visualized during transgastric views of the abdominal aorta. We propose that two‐dimensional and color Doppler echocardiography have several intrinsic advantages over computed tomography, magnetic resonance angiography and catheterization when assessing aortic and visceral arterial pathology.     

Hypertension prevalence and control among community‐dwelling lebanese older adults

There is a high prevalence of hypertension among Lebanese adults, but no evidence is available on its prevalence and control exclusively among older adults (65 + years). This study provides the first evidence on a representative sample of 502 community elderly and presents the basis for future research and policy implications. Results show an overall prevalence of 52% with a significantly higher female‐to‐male ratio. Factors independently associated with hypertension were older age, body mass index, and dementia. More than a third of those with a positive history of hypertension had uncontrolled blood levels. Uncontrolled hypertension was higher among women. Increasing awareness about medication adherence and controlling multi‐morbidities constitute promising measures to lowering the burden of hypertension among Lebanese older adults, especially women.     

Cigarette smoking and associated risk of multiple sclerosis in the Iranian population

Exposure to cigarette smoke is emerging as an environmental risk factor for multiple sclerosis (MS). We investigated the possible association between environmental tobacco smoke, its cumulative exposure, and MS risk. We used data from the Iranian Multiple Sclerosis Registry to identify a case-control of 662 patients who had MS and a comparison group of 394 patients. Information regarding current smoking status, including the number of cigarettes smoked per day, duration, and smoking pack-years indicative of cumulative dose of tobacco smoked was obtained. We analyzed the incidence of MS among ever–smokers who had been smokers during their disease course and prior to disease onset in comparison with never–smokers who had never been exposed by calculating the odds ratio (OR) with a 95% confidence interval (CI) employing logistic regression. Of the 662 MS patients, there were 523 women (79.0%) and 139 men (21.0%), with a mean age of 31 ± 10.0 years at disease onset. The risk for MS was increased among ever–smokers (OR = 1.78, 95% CI = 1.22–2.59, p = 0.03) compared to never–smokers. As compared with never smokers, the OR for patients with 6–10 pack years was 2.91 for men (95% CI = 1.11–9.47, p = 0.03) and 1.69 for women (95% CI = 1.02–6.45, p = 0.04). Our results demonstrate that cigarette smoking is significantly associated with an increased risk for MS. The risk effects of smoking were more noticeable in male patients and at higher tobacco doses.     

Observation on the ultrastructure morphology of HeLa cells treated with ethanol: Statistical analysis

It is estimated that 5.9% of all human deaths are attributable to alcohol consumption and that the harmful use of ethanol ranks among the top five risk factors for causing disease, disability, and death worldwide. Ethanol is known to disrupt phospholipid packing and promote membrane hemifusion at lipid bilayers. With the exception of mitochondria involved in hormone synthesis, the sterol content of mitochondrial membranes is low. As membranes that are low in cholesterol have increased membrane fluidity and are the most easily disordered by ethanol, we hypothesize that mitochondria are sensitive targets for ethanol damage. HeLa cells were exposed to 50 mM ethanol and the direct effects of ethanol on cellular ultrastructure were examined utilizing transmission electron microscopy. Our ultramicroscopic analysis revealed that cells exposed to ethanol harbor fewer incidence of apoptotic morphology; however, significant alterations to mitochondria and to nuclei occurred. We observed statistical increases in the amount of irregular cells and cells with multiple nuclei, nuclei harboring indentations, and nuclei with multiple nucleolus-like bodies. Indeed, our analysis revealed that mitochondrial damage is the most extensive type of cellular damage. Rupturing of cristae was the most prominent damage followed by mitochondrial swelling. Ethanol exposure also resulted in increased amounts of mitochondrial rupturing, organelles with linked membranes, and mitochondria localizing to indentations of nuclear membranes. We theorize that these alterations could contribute to cellular defects in oxidative phosphorylation and, by extension, the inability to generate regular levels of cellular adenosine triphosphate.     

Fast Monte Carlo based joint iterative reconstruction for simultaneous 99mTc/ 123I SPECT imaging

Simultaneous 99mTC/ 123I SPECT allows the assessment of two physiological functions under identical conditions. The separation of these radionuclides is difficult, however, because their energies are close. Most energy-window-based scatter correction methods do not fully model either physical factors or patient-specific activity and attenuation distributions. We have developed a fast Monte Carlo (MC) simulation-based multiple-radionuclide and multiple-energy joint ordered-subset expectation-maximization (JOSEM) iterative reconstruction algorithm, MC-JOSEM. MC-JOSEM simultaneously corrects for scatter and cross talk as well as detector response within the reconstruction algorithm. We evaluated MC-JOSEM for simultaneous brain profusion (99mTc-HMPAO) and neurotransmission (123I-altropane) SPECT. MC simulations of 99mTc and 123I studies were generated separately and then combined to mimic simultaneous 99mTc/ 123I SPECT. All the details of photon transport through the brain, the collimator, and detector, including Compton and coherent scatter, septal penetration, and backscatter from components behind the crystal, were modeled. We reconstructed images from simultaneous dual-radionuclide projections in three ways. First, we reconstructed the photopeak-energy-window projections (with an asymmetric energy window for 1231) using the standard ordered-subsets expectation-maximization algorithm (NSC-OSEM). Second, we used standard OSEM to reconstruct 99mTc photopeak-energy-window projections, while including an estimate of scatter from a Compton-scatter energy window (SC-OSEM). Third, we jointly reconstructed both 99mTc and 123I images using projection data associated with two photo-peak energy windows and an intermediate-energy window using MC-JOSEM. For 15 iterations of reconstruction, the bias and standard deviation of 99mTc activity estimates in several brain structures were calculated for NSC-OSEM, SC-OSEM, and MC-JOSEM, using images reconstructed from primary (unscattered) photons as a reference. Similar calculations were performed for 123I images for NSC-OSEM and MC-JOSEM. For 123I images, dopamine binding potential (BP) at equilibrium and its signal-to-noise ratio (SNR) were also calculated. Our results demonstrate that MC-JOSEM performs better than NSC- and SC-OSEM for quantitation tasks. After 15 iterations of reconstruction, the relative bias of 99mTc activity estimates in the thalamus, striata, white matter, and gray matter volumes from MC-JOSEM ranged from -2.4% to 1.2%, while the same estimates for NSC-OSEM (SC-OSEM) ranged from 20.8% to 103.6% (7.2% to 41.9%). Similarly, the relative bias of 123I activity estimates from 15 iterations of MC-JOSEM in the striata and background ranged from -1.4% to 2.9%, while the same estimates for NSC-OSEM ranged from 1.6% to 10.0%. The relative standard deviation of 99mTc activity estimates from MC-JOSEM ranged from 1.1% to 4.8% versus 1.2% to 6.7% (1.2% to 5.9%) for NSC-OSEM (SC-OSEM). The relative standard deviation of 123I activity estimates using MC-JOSEM ranged from 1.1% to 1.9% versus 1.5% to 2.7% for NSC-OSEM. Using the 123I dopamine BP obtained from the reconstruction produced by primary photons as a reference, the result for MC-JOSEM was 50.5% closer to the reference than that of NSC-OSEM after 15 iterations. The SNR for dopamine BP was 23.6 for MC-JOSEM as compared to 18.3 for NSC-OSEM.     

Grafted human chorionic stem cells restore motor function and preclude cerebellar neurodegeneration in rat model of cerebellar ataxia

Metabolic Brain Disease - Cerebellar ataxia (CA) is a form of ataxia that adversely affects the cerebellum. Cell replacement therapy (CRT) has been considered as a potential treatment for...