JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Right ventricular septal pacing as alternative for failed left ventricular lead implantation in cardiac resynchronization therapy candidates.
Europace
PUBLISHED: 11-01-2014
Show Abstract
Hide Abstract
To compare the effects on left ventricular (LV) function of right ventricular (RV) septal pacing vs. cardiac resynchronization therapy (CRT) in patients with an indication for the latter. Cardiac resynchronization therapy is an effective therapy in patients with drug-refractory heart failure. Despite advances in implantation techniques, LV lead placement can be impossible in up to 10% of cases. We, therefore, assessed the effects of RV septal pacing from mid septum (RVmIVS) and outflow tract (RVOT) on cardiac performance, in comparison with CRT.
Related JoVE Video
Prognostic Value of Rubidium-82 Positron Emission Tomography in Patients After Heart Transplant.
Circ Cardiovasc Imaging
PUBLISHED: 09-02-2014
Show Abstract
Hide Abstract
Cardiac allograft vasculopathy is a key prognostic determinant after heart transplant. Detection and risk stratification of patients with cardiac allograft vasculopathy are problematic. Positron emission tomography using rubidium-82 allows quantification of absolute myocardial blood flow and may have utility for risk stratification in this population.
Related JoVE Video
Automated movement correction for dynamic PET/CT images: evaluation with phantom and patient data.
PLoS ONE
PUBLISHED: 08-11-2014
Show Abstract
Hide Abstract
Head movement during a dynamic brain PET/CT imaging results in mismatch between CT and dynamic PET images. It can cause artifacts in CT-based attenuation corrected PET images, thus affecting both the qualitative and quantitative aspects of the dynamic PET images and the derived parametric images. In this study, we developed an automated retrospective image-based movement correction (MC) procedure. The MC method first registered the CT image to each dynamic PET frames, then re-reconstructed the PET frames with CT-based attenuation correction, and finally re-aligned all the PET frames to the same position. We evaluated the MC method's performance on the Hoffman phantom and dynamic FDDNP and FDG PET/CT images of patients with neurodegenerative disease or with poor compliance. Dynamic FDDNP PET/CT images (65 min) were obtained from 12 patients and dynamic FDG PET/CT images (60 min) were obtained from 6 patients. Logan analysis with cerebellum as the reference region was used to generate regional distribution volume ratio (DVR) for FDDNP scan before and after MC. For FDG studies, the image derived input function was used to generate parametric image of FDG uptake constant (Ki) before and after MC. Phantom study showed high accuracy of registration between PET and CT and improved PET images after MC. In patient study, head movement was observed in all subjects, especially in late PET frames with an average displacement of 6.92 mm. The z-direction translation (average maximum = 5.32 mm) and x-axis rotation (average maximum = 5.19 degrees) occurred most frequently. Image artifacts were significantly diminished after MC. There were significant differences (P<0.05) in the FDDNP DVR and FDG Ki values in the parietal and temporal regions after MC. In conclusion, MC applied to dynamic brain FDDNP and FDG PET/CT scans could improve the qualitative and quantitative aspects of images of both tracers.
Related JoVE Video
Life extension factor klotho enhances cognition.
Cell Rep
PUBLISHED: 01-10-2014
Show Abstract
Hide Abstract
Aging is the primary risk factor for cognitive decline, an emerging health threat to aging societies worldwide. Whether anti-aging factors such as klotho can counteract cognitive decline is unknown. We show that a lifespan-extending variant of the human KLOTHO gene, KL-VS, is associated with enhanced cognition in heterozygous carriers. Because this allele increased klotho levels in serum, we analyzed transgenic mice with systemic overexpression of klotho. They performed better than controls in multiple tests of learning and memory. Elevating klotho in mice also enhanced long-term potentiation, a form of synaptic plasticity, and enriched synaptic GluN2B, an N-methyl-D-aspartate receptor (NMDAR) subunit with key functions in learning and memory. Blockade of GluN2B abolished klotho-mediated effects. Surprisingly, klotho effects were evident also in young mice and did not correlate with age in humans, suggesting independence from the aging process. Augmenting klotho or its effects may enhance cognition and counteract cognitive deficits at different life stages.
Related JoVE Video
Modifiable risk factors for Alzheimer disease and subjective memory impairment across age groups.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Previous research has identified modifiable risk factors for Alzheimer's disease (AD) in older adults. Research is limited on the potential link between these risk factors and subjective memory impairment (SMI), which may precede AD and other dementias. Examination of these potential relationships may help identify those at risk for AD at a stage when interventions may delay or prevent further memory problems. The objective of this study was to determine whether risk factors for AD are associated with SMI among different age groups.
Related JoVE Video
A single slice measure of epicardial adipose tissue can serve as an indirect measure of total epicardial adipose tissue burden and is associated with obstructive coronary artery disease.
Eur Heart J Cardiovasc Imaging
PUBLISHED: 10-09-2013
Show Abstract
Hide Abstract
To evaluate the practical use of the single slice measurement of epicardial adipose tissue (EAT) at the level of the left main coronary artery (EATLM) in predicting the presence of obstructive coronary artery disease (CAD).
Related JoVE Video
Quantifying coronary artery calcification from a contrast-enhanced cardiac computed tomography angiography study.
Eur Heart J Cardiovasc Imaging
PUBLISHED: 08-13-2013
Show Abstract
Hide Abstract
We sought to quantify coronary artery calcium (CAC) using a single contrast-enhanced cardiac computed tomography angiography (CCTA) study. CCTA has been successfully used for the assessment of coronary artery stenoses, whereas non-contrast ECG-gated computed tomography (Standard-CAC) is commonly performed to quantify CAC. Thus each scan individually contributes to the total radiation dose.Methods resultsPatients who underwent both Standard-CAC and CCTA scans were identified. Standard-CAC images were scored using the Agatston method. CCTA scans were scored for CAC (CCTA-CAC), whereby CAC was defined as plaque with attenuation 2 SD above the mean attenuation value of the ascending aorta (HUaorta). The correlation between Standard-CAC and CCTA-CAC was determined with the slope used to derive a correction factor for the conversion of CCTA-CAC results to a Standard-CAC Agatston score (AS). To test applicability, the correction factor was assessed in a separate validation cohort of similar demographics. From April 2011 to June 2012, a derivation cohort of 92 patients was identified and analysed. An additional 47 patients were identified for the validation cohort. Correlation between Standard-CAC and CCTA-CAC was excellent (r = 0.96). The slope (y = 2.74 × CCTA-CAC score) derived correction factor from the derivation cohort was used to adjust CCTA-CAC derived scores to an AS (CCTA-CACcorrected = 2.74 × CCTA-CAC). The correction factor was applied to the validation cohort CCTA-CAC results with excellent agreement between CCTA-CACcorrected and Standard-CAC (kappa = 0.93).
Related JoVE Video
Quantitative determination of methanol and ethanol with synthetic calibration spectra in passive Fourier transform infrared remote sensing measurements.
Appl Spectrosc
PUBLISHED: 07-24-2013
Show Abstract
Hide Abstract
A spectral synthesis strategy is introduced to help obtain estimates of path-integrated concentrations in passive Fourier transform infrared (FT-IR) remote sensing measurements conducted during field-monitoring experiments. Obtaining quantitative information from passive infrared data is challenging because of the joint effects of temperature and concentration on spectral intensities. The collection of calibration data for use in modeling spectral intensities for a given set of experimental conditions is also costly and labor intensive. In the work presented here, a radiance model is defined for use in synthesizing calibration spectra that serve as inputs to partial least-squares (PLS) models that relate spectral intensities to path-integrated concentrations. The field data for which quantitative estimates are desired are used to estimate the background temperature associated with a given time and set of experimental conditions. Sample temperatures can be obtained through either experimental measurement or by estimating one calibration release. Given these temperatures, calibration data can be synthesized and the PLS model developed. This methodology is tested with stack monitoring data obtained from controlled releases of pure and mixture samples of heated ethanol and methanol. Experiments were conducted across 6 days with stack temperatures of 150 to 200 °C and with path-integrated concentrations in the range of 10 to 300 parts per million meters. Median relative errors in the estimates of path-integrated concentration were typically in the range of 20% or less, with the best results observed at the higher stack temperatures.
Related JoVE Video
Lessons from the Tc-99m shortage: implications of substituting Tl-201 for Tc-99m single-photon emission computed tomography.
Circ Cardiovasc Imaging
PUBLISHED: 07-19-2013
Show Abstract
Hide Abstract
In 2009, the Chalk River nuclear reactor closed for repairs that led to a critical shortage of technetium-99m (Tc-99m). Several centers used thallium-201 (Tl-201) as an alternative radiotracer for myocardial perfusion imaging. Because Tl-201 is considered by many as a suboptimal radiotracer, we sought to understand the impact of using Tl-201 (during the Tc-99m shortage) on downstream resource utilization.
Related JoVE Video
Psychological Well-Being and Regional Brain Amyloid and Tau in Mild Cognitive Impairment.
Am J Geriatr Psychiatry
PUBLISHED: 03-26-2013
Show Abstract
Hide Abstract
OBJECTIVES: To determine whether psychological well-being in people with mild cognitive impairment (MCI), a risk state for Alzheimer disease (AD), is associated with in vivo measures of brain pathology. METHODS: Cross-sectional clinical assessments and positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[F18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles, were performed on middle-aged and older adults at a university research institute. Volunteers were aged 40-85 years with MCI (N = 35) or normal cognition (N = 29) without depression or anxiety. Statistical analyses included general linear models, using regional FDDNP-PET binding values as dependent variables and the Vigor-Activity subscale of the Profile of Mood States (POMS) as the independent variable, covarying for age. The POMS is a self-rated inventory of 65 adjectives that describe positive and negative feelings. RESULTS: Scores on the POMS Vigor-Activity subscale were inversely associated with degree of FDDNP binding in the posterior cingulate cortex (r = -0.35, p = 0.04) in the MCI group but not in the control group. CONCLUSION: Psychological well-being, as indicated by self-reports of greater vigor and activity, is associated with lower FDDNP-PET binding in the posterior cingulate cortex, a region involved in emotional regulation, in individuals with MCI but not in those with normal cognition. These findings are consistent with previous work indicating that deposition of brain amyloid plaques and tau tangles may result in noncognitive and cognitive symptoms in persons at risk for AD.
Related JoVE Video
Pomegranate juice augments memory and FMRI activity in middle-aged and older adults with mild memory complaints.
Evid Based Complement Alternat Med
PUBLISHED: 03-17-2013
Show Abstract
Hide Abstract
Despite increasing emphasis on the potential of dietary antioxidants in preventing memory loss and on diet as a precursor of neurological health, rigorous studies investigating the cognitive effects of foods and their components are rare. Recent animal studies have reported memory and other cognitive benefits of polyphenols, found abundantly in pomegranate juice. We performed a preliminary, placebo-controlled randomized trial of pomegranate juice in older subjects with age-associated memory complaints using memory testing and functional brain activation (fMRI) as outcome measures. Thirty-two subjects (28 completers) were randomly assigned to drink 8 ounces of either pomegranate juice or a flavor-matched placebo drink for 4 weeks. Subjects received memory testing, fMRI scans during cognitive tasks, and blood draws for peripheral biomarkers before and after the intervention. Investigators and subjects were all blind to group membership. After 4 weeks, only the pomegranate group showed a significant improvement in the Buschke selective reminding test of verbal memory and a significant increase in plasma trolox-equivalent antioxidant capacity (TEAC) and urolithin A-glucuronide. Furthermore, compared to the placebo group, the pomegranate group had increased fMRI activity during verbal and visual memory tasks. While preliminary, these results suggest a role for pomegranate juice in augmenting memory function through task-related increases in functional brain activity.
Related JoVE Video
APOE associated hemispheric asymmetry of entorhinal cortical thickness in aging and Alzheimers disease.
Psychiatry Res
PUBLISHED: 02-27-2013
Show Abstract
Hide Abstract
Across species structural and functional hemispheric asymmetry is a fundamental feature of the brain. Environmental and genetic factors determine this asymmetry during brain development and modulate its interaction with brain disorders. The e4 allele of the apolipoprotein E gene (APOE-4) is a risk factor for Alzheimers disease, associated with regionally specific effects on brain morphology and function during the life span. Furthermore, entorhinal and hippocampal hemispheric asymmetry could be modified by pathology during Alzheimers disease development. Using high-resolution magnetic resonance imaging and a cortical unfolding technique we investigated whether carrying the APOE-4 allele influences hemispheric asymmetry in the entorhinal cortex and the hippocampus among patients with Alzheimers disease as well as in middle-aged and older cognitively healthy individuals. APOE-4 carriers showed a thinner entorhinal cortex in the left hemisphere when compared with the right hemisphere across all participants. Non-carriers of the allele showed this asymmetry only in the patient group. Cortical thickness in the hippocampus did not vary between hemispheres among APOE-4 allele carriers and non-carriers. The APOE-4 allele modulates hemispheric asymmetry in entorhinal cortical thickness. Among Alzheimers disease patients, this asymmetry might be less dependent on the APOE genotype and a more general marker of incipient disease pathology.
Related JoVE Video
Healthy behavior and memory self-reports in young, middle-aged, and older adults.
Int Psychogeriatr
PUBLISHED: 02-21-2013
Show Abstract
Hide Abstract
Previous research has shown that healthy behaviors, such as regular physical exercise, a nutritious diet, and not smoking, are associated with a lower risk for Alzheimers disease and dementia. However, less is known about the potential link between healthy behaviors and mild memory symptoms that may precede dementia in different age groups.
Related JoVE Video
PET scanning of brain tau in retired national football league players: preliminary findings.
Am J Geriatr Psychiatry
PUBLISHED: 01-22-2013
Show Abstract
Hide Abstract
Mild traumatic brain injury due to contact sports may cause chronic behavioral, mood, and cognitive disturbances associated with pathological deposition of tau protein found at brain autopsy. To explore whether brain tau deposits can be detected in living retired players, we used positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP).
Related JoVE Video
KIAA1462, A Coronary Artery Disease Associated Gene, Is a Candidate Gene for Late Onset Alzheimer Disease in APOE Carriers.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Alzheimer disease (AD) is a devastating neurodegenerative disease affecting more than five million Americans. In this study, we have used updated genetic linkage data from chromosome 10 in combination with expression data from serial analysis of gene expression to choose a new set of thirteen candidate genes for genetic analysis in late onset Alzheimer disease (LOAD). Results in this study identify the KIAA1462 locus as a candidate locus for LOAD in APOE4 carriers. Two genes exist at this locus, KIAA1462, a gene associated with coronary artery disease, and "rokimi", encoding an untranslated spliced RNA The genetic architecture at this locus suggests that the gene product important in this association is either "rokimi", or a different isoform of KIAA1462 than the isoform that is important in cardiovascular disease. Expression data suggests that isoform f of KIAA1462 is a more attractive candidate for association with LOAD in APOE4 carriers than "rokimi" which had no detectable expression in brain.
Related JoVE Video
Brain network local interconnectivity loss in aging APOE-4 allele carriers.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 11-21-2011
Show Abstract
Hide Abstract
Old age and possession of the APOE-4 allele are the two main risk factors for developing later onset Alzheimers Disease (AD). Carriers of the APOE-4 allele have known differences in intrinsic functional brain network activity across the life span. These individuals also demonstrate specific regional differences in gray and white matter gross structure. However, the relationship of these variations to whole brain structural network connectivity remains unclear. We performed diffusion tensor imaging (DTI), T1 structural imaging, and cognitive testing on aging APOE-4 noncarriers (n = 30; mean age = 63.8±8.3) and APOE-4 carriers (n = 25; mean age = 60.8 ±9.7). Fiber tractography was used to derive whole brain structural graphs, and graph theory was applied to assess structural network properties. Network communication efficiency was determined for each network by quantifying local interconnectivity, global integration, and the balance between these, the small worldness. Relative to noncarriers, APOE-4 carriers demonstrated an accelerated age-related loss of mean local interconnectivity (r = -0.64, P ? 0.01) and regional local interconnectivity decreases in the precuneus (r = -0.64), medial orbitofrontal cortex (r = -0.5), and lateral parietal cortex (r = -0.54). APOE-4 carriers also showed significant age-related loss in mean cortical thickness (r = -0.52, P < 0.05). Cognitively, APOE-4 carriers had significant negative correlations of age and performance on two episodic memory tasks (P < 0.05). This genotype-specific pattern of structural connectivity change with age thus appears related to changes in gross cortical structure and cognition, potentially affecting the rate and/or spatial distribution of AD-related pathology.
Related JoVE Video
Comparative evaluation of Logan and relative-equilibrium graphical methods for parametric imaging of dynamic [18F]FDDNP PET determinations.
Neuroimage
PUBLISHED: 11-11-2011
Show Abstract
Hide Abstract
Logan graphical analysis with cerebellum as reference region has been widely used for the estimation of the distribution volume ratio (DVR) of [(18)F]FDDNP as a measure of amyloid burden and tau deposition in human brain because of its simplicity and computational ease. However, spurious parametric DVR images may be produced with shorter scanning times and when the noise level is high. In this work, we have characterized a relative-equilibrium-based (RE) graphical method against the Logan analysis for parametric imaging and region-of-interest (ROI) analysis.
Related JoVE Video
Protein binding in patients with late-life depression.
Arch. Gen. Psychiatry
PUBLISHED: 11-09-2011
Show Abstract
Hide Abstract
Depression has been identified as a risk factor and a prodrome of dementia. Common neurobiological mechanisms may underlie this clinical and phenomenologic overlap.
Related JoVE Video
Determining patient prognosis using computed tomography coronary angiography.
Expert Rev Med Devices
PUBLISHED: 10-27-2011
Show Abstract
Hide Abstract
In addition to demonstrating luminal narrowings, cardiac computed tomography angiography (CTA) has the ability to detect nonstenotic plaque, vessel wall calcification and can assess left ventricular function. CTA prognostic studies have considered these components individually and in combination to produce novel risk factor scores to help predict clinical outcomes. In this article, we will consider the utility of CTA to predict clinical risk by considering the evidence for luminal stenosis, plaque scores, plaque descriptors and models combining these elements. We will also discuss some of the emerging applications of CTA that will likely provide future prognostic data in coronary artery disease patients. Although initially described as an anatomical investigation to determine the presence of coronary disease, CTA is being explored as a tool for functional imaging and may soon provide a noninvasive technique of anatomical and functional assessment previously only possible by invasive methods.
Related JoVE Video
Impact of temporary right ventricular pacing from different sites on echocardiographic indices of cardiac function.
Europace
PUBLISHED: 07-14-2011
Show Abstract
Hide Abstract
To assess the impact of pacing from different right ventricular (RV) pacing sites on left ventricular (LV) function. Chronic apical RV pacing may induce heart failure. To reduce this RV, mid-septum and outflow tract are suggested as alternative pacing sites. We therefore assessed cardiac performance during temporary RV pacing from apical vs. mid-septum or outflow tract sites, using echocardiography and electrocardiography.
Related JoVE Video
Incremental prognostic value of cardiac computed tomography in coronary artery disease using CONFIRM: COroNary computed tomography angiography evaluation for clinical outcomes: an InteRnational Multicenter registry.
Circ Cardiovasc Imaging
PUBLISHED: 07-05-2011
Show Abstract
Hide Abstract
Large multicenter studies validating the prognostic value of coronary computed tomographic angiography (CCTA) and left ventricular ejection fraction (LVEF) are lacking. We sought to confirm the independent and incremental prognostic value of coronary artery disease (CAD) severity measured using 64-slice CCTA over LVEF and clinical variables.
Related JoVE Video
Positron emission tomography of brain ?-amyloid and ? levels in adults with Down syndrome.
Arch. Neurol.
PUBLISHED: 06-15-2011
Show Abstract
Hide Abstract
To determine the neuropathological load in the living brain of nondemented adults with Down syndrome using positron emission tomography with 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([(18)F]FDDNP) and to assess the influence of age and cognitive and behavioral functioning. For reference, [(18)F]FDDNP binding values and patterns were compared with those from patients with Alzheimer disease and cognitively intact control participants.
Related JoVE Video
Established and emerging dose reduction methods in cardiac computed tomography.
J Nucl Cardiol
PUBLISHED: 06-02-2011
Show Abstract
Hide Abstract
Cardiac computed tomography (CT) is a non-invasive modality that is commonly used as an alternative to invasive coronary angiography for the investigation of coronary artery disease. The enthusiasm for this technology has been tempered by a growing appreciation of the potential risks of malignancy associated with the use of ionising radiation. In the spirit of minimizing patient risk, the medical profession and industry have worked hard to developed methods and protocols to reduce patient radiation exposure while maintaining excellent diagnostic accuracy. A complete understanding of radiation reduction techniques will allow clinicians to reduce patient risk while providing an important diagnostic service. This review will consider the established and emerging techniques that may be adopted to reduce patient absorbed doses from x-ray CT. By modifying (1) x-ray tube output, (2) imaging time (scan duration), (3) imaging distance (scan length) and (4) the appropriate use of shielding, clinicians will be able to adhere to the as low as reasonably achievable (ALARA) principle.
Related JoVE Video
PET imaging of aortic atherosclerosis: Is combined imaging of plaque anatomy and function an amaranthine quest or conceivable reality?
J Nucl Cardiol
PUBLISHED: 05-10-2011
Show Abstract
Hide Abstract
Traditionally, blood vessels have been studied using contrast luminography to determine the site, extent and severity of luminal compromise by atherosclerotic deposits. Similar anatomical data can now be acquired non-invasively using ultrasound, computed tomography or magnetic resonance imaging. Plaque stability is an important determinant of subsequent vascular events and currently functional data on the stability of plaque is less well provided by these methods. The search for non-invasive techniques to image combined plaque anatomy and function has been pursued with visionary anticipation. This expectation may soon be realised as imaging with radionuclide-labelled atheroma-targeted contrast agents has demonstrated that plaque functional characteristics can now be shown. Increasingly positron emission tomography/computed tomography (PET/CT) imaging with (18)F fluorodexoyglucose (FDG) and other radionuclides is being used to determine culprit plaques in complex clinically scenarios. Clinically, this information may prove extremely valuable in the assessment of stable and unstable patients and its use in prime time medical practice is eagerly awaited. We will discuss the current clinical applications of functional atheroma imaging in the aorta and highlight the promising preclinical data on novel image biomarkers of plaque instability. If clinical science is able to successfully translate these advances in vascular imaging from the bench to the bedside, a new paradigm will be achieved in cardiovascular diagnostics.
Related JoVE Video
[F-18]FDDNP microPET imaging correlates with brain A? burden in a transgenic rat model of Alzheimer disease: effects of aging, in vivo blockade, and anti-A? antibody treatment.
Neurobiol. Dis.
PUBLISHED: 04-27-2011
Show Abstract
Hide Abstract
In vivo detection of Alzheimers disease (AD) neuropathology in living patients using positron emission tomography (PET) in conjunction with high affinity molecular imaging probes for ?-amyloid (A?) and tau has the potential to assist with early diagnosis, evaluation of disease progression, and assessment of therapeutic interventions. Animal models of AD are valuable for exploring the in vivo binding of these probes, particularly their selectivity for specific neuropathologies, but prior PET experiments in transgenic mice have yielded conflicting results. In this work, we utilized microPET imaging in a transgenic rat model of brain A? deposition to assess [F-18]FDDNP binding profiles in relation to age-associated accumulation of neuropathology. Cross-sectional and longitudinal imaging demonstrated that [F-18]FDDNP binding in the hippocampus and frontal cortex progressively increases from 9 to 18months of age and parallels age-associated A? accumulation. Specificity of in vivo [F-18]FDDNP binding was assessed by naproxen pretreatment, which reversibly blocked [F-18]FDDNP binding to A? aggregrates. Both [F-18]FDDNP microPET imaging and neuropathological analyses revealed decreased A? burden after intracranial anti-A? antibody administration. The combination of this non-invasive imaging method and robust animal model of brain A? accumulation allows for future longitudinal in vivo assessments of potential therapeutics for AD that target A? production, aggregation, and/or clearance. These results corroborate previous analyses of [F-18]FDDNP PET imaging in clinical populations.
Related JoVE Video
Prognostic value of CT angiography in coronary bypass patients.
JACC Cardiovasc Imaging
PUBLISHED: 01-14-2011
Show Abstract
Hide Abstract
We sought the incremental prognostic value of coronary computed tomography angiography (CTA) in coronary artery bypass graft (CABG) patients.
Related JoVE Video
Prevention in psychiatry: effects of healthy lifestyle on cognition.
Psychiatr. Clin. North Am.
PUBLISHED: 12-16-2010
Show Abstract
Hide Abstract
People are living longer than ever. With greater longevity, a critical question becomes whether or not our memories endure across the life span. This article reviews the common forms of age-related memory change and the emerging evidence related to putative risk and protective factors for brain aging. With increasing awareness of Alzheimer disease and related dementias, patients, families, and clinicians are eager for concise and accurate information about the effects and limitations of preventative strategies related to lifestyle choices that may improve cognitive health.
Related JoVE Video
Synthetic training sets for the development of discriminant functions for the detection of volatile organic compounds from passive infrared remote sensing data.
Analyst
PUBLISHED: 10-18-2010
Show Abstract
Hide Abstract
A novel synthetic data generation methodology is described for use in the development of pattern recognition classifiers that are employed for the automated detection of volatile organic compounds (VOCs) during infrared remote sensing measurements. The approach used is passive Fourier transform infrared spectrometry implemented in a downward-looking mode on an aircraft platform. A key issue in developing this methodology in practice is the need for example data that can be used to train the classifiers. To replace the time-consuming and costly collection of training data in the field, this work implements a strategy for taking laboratory analyte spectra and superimposing them on background spectra collected from the air. The resulting synthetic spectra can be used to train the classifiers. This methodology is tested by developing classifiers for ethanol and methanol, two prevalent VOCs in wide industrial use. The classifiers are successfully tested with data collected from the aircraft during controlled releases of ethanol and during a methanol release from an industrial facility. For both ethanol and methanol, missed detections in the aircraft data are in the range of 4 to 5%, with false positive detections ranging from 0.1 to 0.3%.
Related JoVE Video
Family history of Alzheimers disease and hippocampal structure in healthy people.
Am J Psychiatry
PUBLISHED: 08-04-2010
Show Abstract
Hide Abstract
Structural brain changes appear years before the onset of Alzheimers disease, the leading cause of dementia late in life. Determining risk factors for such presymptomatic brain changes may assist in identifying candidates for future prevention treatment trials. In addition to the e4 allele of the apolipoprotein E gene (APOE-4), the major known genetic risk factor, a family history of Alzheimers disease also increases the risk to develop the disease, reflecting yet unidentified genetic and, perhaps, nongenetic risks. The authors investigated the influence of APOE-4 genotype and family history risks on cortical thickness in medial temporal lobe subregions among volunteers without cognitive impairment.
Related JoVE Video
Biochemical, neuropathological, and neuroimaging characteristics of early-onset Alzheimers disease due to a novel PSEN1 mutation.
Neurosci. Lett.
PUBLISHED: 06-16-2010
Show Abstract
Hide Abstract
Familial Alzheimers disease (AD) due to PSEN1 mutations provides an opportunity to examine AD biomarkers in persons in whom the diagnosis is certain. We describe a 55 year-old woman with clinically probable AD and a novel PSEN1 mutation who underwent genetic, clinical, biochemical and magnetic resonance and nuclear imaging assessments. We also describe neuropathological findings in her similarly affected brother. Neuropsychological testing confirmed deficits in memory, visuospatial and language function. CSF t-tau and p-tau181 were markedly elevated and A?(42) levels reduced. FDG-PET revealed hypometabolism in the left parietotemporal cortex. FDDNP-PET showed increased binding of tracer in medial temporal and parietal lobes and in the head of the caudate and anterior putamen bilaterally. Neuropathological examination of her brother showed the typical findings of AD and the striatum demonstrated amyloid pathology and marked neurofibrillary pathology beyond that typically seen in late-onset AD. A novel S212Y substitution in PSEN1 was present in the index patient and her affected brother but not in an older unaffected sister. An in vitro assay in which the S212Y mutation was introduced in cell culture confirmed that it was associated with increased production of A?(42). We describe biochemical, imaging, and neuropathological changes in a pedigree with a novel PSEN1 mutation. This allows us to validate the pathogenicity of this mutation and the indices used to assess AD.
Related JoVE Video
Improved heart function follows enhanced inflammatory cell recruitment and angiogenesis in 11betaHSD1-deficient mice post-MI.
Cardiovasc. Res.
PUBLISHED: 05-21-2010
Show Abstract
Hide Abstract
Mice unable to locally regenerate corticosterone due to deficiency of 11?-hydroxysteroid dehydrogenase type 1 (11?HSD1) have enhanced angiogenesis during acute myocardial infarct healing. The present study investigates the hypotheses that in these mice (i) inflammation and angiogenic signalling are promoted and (ii) longer-term remodelling and function are improved.
Related JoVE Video
Wavelet analysis used for spectral background removal in the determination of glucose from near-infrared single-beam spectra.
Anal. Chim. Acta
PUBLISHED: 04-26-2010
Show Abstract
Hide Abstract
Wavelet analysis is developed as a preprocessing tool for use in removing background information from near-infrared (near-IR) single-beam spectra before the construction of multivariate calibration models. Three data sets collected with three different near-IR spectrometers are investigated that involve the determination of physiological levels of glucose (1-30 mM) in a simulated biological matrix containing alanine, ascorbate, lactate, triacetin, and urea in phosphate buffer. A factorial design is employed to optimize the specific wavelet function used and the level of decomposition applied, in addition to the spectral range and number of latent variables associated with a partial least-squares calibration model. The prediction performance of the computed models is studied with separate data acquired after the collection of the calibration spectra. This evaluation includes one data set collected over a period of more than 6 months. Preprocessing with wavelet analysis is also compared to the calculation of second-derivative spectra. Over the three data sets evaluated, wavelet analysis is observed to produce better-performing calibration models, with improvements in concentration predictions on the order of 30% being realized relative to models based on either second-derivative spectra or spectra preprocessed with simple additive and multiplicative scaling correction. This methodology allows the construction of stable calibrations directly with single-beam spectra, thereby eliminating the need for the collection of a separate background or reference spectrum.
Related JoVE Video
Therapeutics for cognitive aging.
Ann. N. Y. Acad. Sci.
PUBLISHED: 04-16-2010
Show Abstract
Hide Abstract
This review summarizes the scientific talks presented at the conference "Therapeutics for Cognitive Aging," hosted by the New York Academy of Sciences and the Alzheimers Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia, as well as by a number of lay people-approximately 200 in all-the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease.
Related JoVE Video
Specific estrogen sulfotransferase (SULT1E1) substrates and molecular imaging probe candidates.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 03-19-2010
Show Abstract
Hide Abstract
This work focuses on the development of specific substrates for estrogen sulfotransferase (SULT1E1) to produce molecular imaging probes for this enzyme. SULT1E1 is a key enzyme in estrogen homeostasis, playing a central role in the prevention and development of human disease. In vitro sulfation assays showed alkyl and aryl substitutions to a fused heterocyclic system modeled after beta-naphthol (betaN), based on compounds that interact with the estrogen receptor, rendered several molecules with enhanced specificity for SULT1E1 over SULT1A1*1, SULT1A1*2, SULT1A3, and SULT2A1. Several 6-hydroxy-2-arylbenzothiazoles tested demonstrated excellent affinity--V(max)/K(m) ratios-and specificity for SULT1E1. K(m) values ranged from 0.12-2.36 microM. A strong correlation was observed between polarity of the 4-sustituent on the 2-aryl moiety (Hammett sigma(p)) and the log(V(max)/K(m)) (r = 0.964). Substrate sensitivity is influenced by the acidity of the 6-phenolic group demonstrated by correlating its (1)H NMR chemical shift (delta(OH)) with the log(V(max)/K(m)) (r = 0.963). Acidity is mediated by the electron withdrawing capacity of the 4-substituent outlined by the correlation of the C-2 (13)C NMR chemical shift (delta(C2)) with the log(V(max)/K(m)) (r = 0.987). 2-[4-(Methylamino)phenyl]-6-hydroxybenzothiazole (2b) was radiolabeled with carbon-11 ((11)C-(2b)) and used in vivo for microPET scanning and tissue metabolite identification. High PET signal was paralleled with the presence of radiolabeled (11)C-(2b)-6-O-sulfate and the SULT1E1 protein detected by western blot. Because this and other members of this family presenting specificity for SULT1E1 can be labeled with carbon-11 or fluorine-18, in vivo assays of SULT1E1 functional activity are now feasible in humans.
Related JoVE Video
Longitudinal changes in medial temporal cortical thickness in normal subjects with the APOE-4 polymorphism.
Neuroimage
PUBLISHED: 03-04-2010
Show Abstract
Hide Abstract
People with the apolipoprotein-Eepsilon4 (APOE-4) genetic risk for Alzheimers disease show morphologic differences in medial temporal lobe regions when compared to non-carriers of the allele. Using a high-resolution MRI and cortical unfolding approach, our aim was to determine the rate of cortical thinning among medial temporal lobe subregions over the course of 2 years. We hypothesized that APOE-4 genetic risk would contribute to longitudinal cortical thickness change in the subiculum and entorhinal cortex, regions preferentially susceptible to Alzheimers disease related pathology. Thirty-two cognitively intact subjects, mean age 61 years, 16 APOE-4 carriers, 16 non-carriers, underwent baseline and follow-up MRI scans. Over this relatively brief interval, we found significantly greater cortical thinning in the subiculum and entorhinal cortex of APOE-4 carriers when compared to non-carriers of the allele. Average cortical thinning across all medial temporal lobe subregions combined was also significantly greater for APOE-4 carriers. This finding is consistent with the hypothesis that carrying the APOE-4 allele renders subjects at a higher risk for developing Alzheimers disease.
Related JoVE Video
Pharmacotherapy and other treatments for elderly patients with depression.
J Clin Psychiatry
PUBLISHED: 02-05-2010
Show Abstract
Hide Abstract
Depression in older adults can be difficult to diagnose and a challenge to treat. Clinicians must address treatment issues caused by aging, such as comorbid medical illness, physical limitations, or the presence of cognitive impairments. Proven treatments for depression in older adults include psychotherapy, medications, and electroconvulsive therapy. When choosing therapies for older patients, possible adverse side effects, drug interactions, and patient limitations should guide treatment selection.
Related JoVE Video
Noninvasive assessment of left ventricular filling pressure after acute myocardial infarction: a prospective study of the relative prognostic utility of clinical assessment, echocardiography, and B-type natriuretic peptide.
Am. Heart J.
PUBLISHED: 01-28-2010
Show Abstract
Hide Abstract
Elevated left ventricular filling pressure after acute myocardial infarction (AMI) may be identified using clinical assessment, echocardiography, and B-type natriuretic peptide (BNP) levels. All of these predict outcome in this setting. There are, however, no data assessing their relative prognostic value. The current study addresses this.
Related JoVE Video
Movement correction method for human brain PET images: application to quantitative analysis of dynamic 18F-FDDNP scans.
J. Nucl. Med.
PUBLISHED: 01-15-2010
Show Abstract
Hide Abstract
Head movement during a PET scan (especially a dynamic scan) can affect both the qualitative and the quantitative aspects of an image, making it difficult to accurately interpret the results. The primary objective of this study was to develop a retrospective image-based movement correction (MC) method and evaluate its implementation on dynamic 2-(1-{6-[(2-(18)F-fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ((18)F-FDDNP) PET images of cognitively intact controls and patients with Alzheimers disease (AD).
Related JoVE Video
Reduced hippocampal CA2, CA3, and dentate gyrus activity in asymptomatic people at genetic risk for Alzheimers disease.
Neuroimage
PUBLISHED: 08-31-2009
Show Abstract
Hide Abstract
Previous functional magnetic resonance imaging (MRI) studies in healthy subjects with the apolipoprotein Eepsilon4 (APOE-4) genetic risk for Alzheimers disease have shown increased activation during memory task performance in broadly distributed cortical regions. These findings have been hypothesized to reflect compensatory recruitment of intact brain regions that presumably result from subtle neural dysfunction reflecting incipient disease. In this study, we used high-resolution functional MRI in APOE-4 carriers and non-carriers to measure activity in hippocampal subregions (CA fields 1, 2, 3; dentate gyrus [DG], and subiculum) and adjacent medial temporal lobe (parahippocampal and entorhinal) subregions. We found reduced left CA2, CA3, and dentate gyrus (CA23DG) activity in cognitively intact APOE-4 carriers. These results suggest that reduced neural activity in hippocampal subregions may underlie the compensatory increase in extrahippocampal activity in people with a genetic risk for Alzheimers disease prior to the onset of cognitive deficits.
Related JoVE Video
Quantitative analysis of [18F]FDDNP PET using subcortical white matter as reference region.
Eur. J. Nucl. Med. Mol. Imaging
PUBLISHED: 07-08-2009
Show Abstract
Hide Abstract
Subcortical white matter is known to be relatively unaffected by amyloid deposition in Alzheimers disease (AD). We investigated the use of subcortical white matter as a reference region to quantify [(18)F]FDDNP binding in the human brain.
Related JoVE Video
Design considerations for near-infrared filter photometry: effects of noise sources and selectivity.
Appl Spectrosc
PUBLISHED: 06-18-2009
Show Abstract
Hide Abstract
Optimal filter design of two-channel near-infrared filter photometers is investigated for simulated two-component systems consisting of an analyte and a spectrally overlapping interferent. The degree of overlap between the analyte and interferent bands is varied over three levels. The optimal design is obtained for three cases: a source or background flicker noise limited case, a shot noise limited case, and a detector noise limited case. Conventional photometers consist of narrow-band optical filters with their bands located at discrete wavelengths. However, the use of broadband optical filters with overlapping responses has been proposed to obtain as much signal as possible from a weak and broad analyte band typical of near-infrared absorptions. One question regarding the use of broadband optical filters with overlapping responses is the selectivity achieved by such filters. The selectivity of two-channel photometers is evaluated on the basis of the angle between the analyte and interferent vectors in the space spanned by the relative change recorded for each of the two detector channels. This study shows that for the shot noise limited or detector noise limited cases, the slight decrease in selectivity with the use of broadband optical filters can be compensated by the higher signal-to-noise ratio afforded by the use of such filters. For the source noise limited case, the best quantitative results are obtained with the use of narrow-band non-overlapping optical filters.
Related JoVE Video
Entorhinal cortex structure and functional MRI response during an associative verbal memory task.
Hum Brain Mapp
PUBLISHED: 06-10-2009
Show Abstract
Hide Abstract
Entorhinal cortex (ERC) volume in adults with mild cognitive impairment has been shown to predict prodromal Alzheimers disease (AD). Likewise, neuronal loss in ERC has been associated with AD, but not with normal aging. Because ERC is part of a major pathway modulating input to the hippocampus, structural changes there may result in changes to cognitive performance and functional brain activity during memory tasks. In 32 cognitively intact older adults, we examined the relationship between left ERC thickness and functional magnetic resonance imaging (fMRI) activity during an associative verbal memory task. This task has been shown previously to activate regions that are sensitive to aging and AD risk. ERC was manually defined on native space, high resolution, oblique coronal MRI scans. Subjects having thicker left ERC showed greater activation in anterior cingulate and medial frontal regions during memory retrieval, but not encoding. This result was independent of hippocampal volume. Anterior cingulate cortex is directly connected to ERC, and is, along with medial frontal cortex, implicated in error detection, which is impaired in AD. Our results suggest that in healthy older adults, processes that engage frontal regions during memory retrieval are related to ERC structure.
Related JoVE Video
PET of brain prion protein amyloid in Gerstmann-Sträussler-Scheinker disease.
Brain Pathol.
PUBLISHED: 06-09-2009
Show Abstract
Hide Abstract
In vivo amyloid PET imaging was carried out on six symptomatic and asymptomatic carriers of PRNP mutations associated with the Gerstmann-Sträussler-Scheinker (GSS) disease, a rare familial neurodegenerative brain disorder demonstrating prion amyloid neuropathology, using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP). 2-Deoxy-2-[F-18]fluoro-d-glucose PET ([F-18]FDG) and magnetic resonance imaging (MRI) scans were also performed in each subject. Increased [F-18]FDDNP binding was detectable in cerebellum, neocortex and subcortical areas of all symptomatic gene carriers in close association with the experienced clinical symptoms. Parallel glucose metabolism ([F-18]FDG) reduction was observed in neocortex, basal ganglia and/or thalamus, which supports the close relationship between [F-18]FDDNP binding and neuronal dysfunction. Two asymptomatic gene carriers displayed no cortical [F-18]FDDNP binding, yet progressive [F-18]FDDNP retention in caudate nucleus and thalamus was seen at 1- and 2-year follow-up in the older asymptomatic subject. In vitro FDDNP labeling experiments on brain tissue specimens from deceased GSS subjects not participating in the in vivo studies indicated that in vivo accumulation of [F-18]FDDNP in subcortical structures, neocortices and cerebellum closely related to the distribution of prion protein pathology. These results demonstrate the feasibility of detecting prion protein accumulation in living patients with [F-18]FDDNP PET, and suggest an opportunity for its application to follow disease progression and monitor therapeutic interventions.
Related JoVE Video
Depression and anxiety symptoms are associated with cerebral FDDNP-PET binding in middle-aged and older nondemented adults.
Am J Geriatr Psychiatry
PUBLISHED: 05-28-2009
Show Abstract
Hide Abstract
Amyloid senile plaques and tau neurofibrillary tangles are neuropathologic hallmarks of Alzheimer disease, which may be associated with mild cognitive impairment (MCI) or mood and anxiety symptoms years before the dementia diagnosis. To address this issue, the authors obtained positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), a molecule that binds to amyloid plaques and neurofibrillary tangles, to determine whether symptoms of depression and anxiety in nondemented subjects were associated with increased FDDNP-PET binding values.
Related JoVE Video
Surface feature-guided mapping of cerebral metabolic changes in cognitively normal and mildly impaired elderly.
Mol Imaging Biol
PUBLISHED: 04-28-2009
Show Abstract
Hide Abstract
The aim of this study was to investigate the longitudinal positron emission tomography (PET) metabolic changes in the elderly.
Related JoVE Video
Food-the way to a mans heart: a mini-case series of Campylobacter perimyocarditis.
Scand. J. Infect. Dis.
PUBLISHED: 04-28-2009
Show Abstract
Hide Abstract
Campylobacter jejuni enteritis is 1 of the most common causes of food poisoning. Although an infrequent complication, Campylobacter associated perimyocarditis can have fatal consequences. This article illustrates 2 cases. We examine the types of Campylobacter jejuni responsible and report the observed male preponderance of this complication.
Related JoVE Video
Differential FDDNP PET patterns in nondemented middle-aged and older adults.
Am J Geriatr Psychiatry
PUBLISHED: 04-25-2009
Show Abstract
Hide Abstract
The authors explored whether positron emission tomography (PET) with 2-(1-{6-[(2-[fluorine-18]fluoroethyl)(methyl) amino]-2-naphthyl} ethylidene)malononitrile (FDDNP), a molecule that binds to plaques and tangles in vitro, might identify homogeneous subgroups of persons in middle-aged and older persons with mild cognitive impairment (MCI) or normal cognition.
Related JoVE Video
Thalamo-Basal Ganglia connectivity in postmenopausal women receiving estrogen therapy.
Neurochem. Res.
PUBLISHED: 03-31-2009
Show Abstract
Hide Abstract
Cumulative data on the effects of estrogen therapy (ET) on brain function in postmenopausal women suggests that ET influences cerebral metabolism and may protect against age-related declines in various domains of cognitive function. The beneficial cognitive effects of ET may relate to its modulation of the thalamic-striatum cholinergic and dopaminergic systems, as the activity of both neurotransmitter systems in the thalamus appears to be positively influenced by estrogen. In the current study, we attempted to evaluated regional cerebral brain metabolism utilizing [18F]-fluorodeoxyglucose positron emission tomography in 11 healthy recently-postmenopausal women on ET (ET+) in comparison to 11 recently-postmenopausal and ET-naïve women (ET-) in order to assess the effects of ET on cholinergic and dopaminergic system regulation. Results showed thalamo-basal ganglia connectivity among ET+ women but not among ET- women. The presence of connectivity in the thalamo-striatal pathway in recently postmenopausal women suggests estrogen effects in preserving integrity of the cholinergic and dopaminergic systems. The results also suggest that ET initiated at or near the menopausal transition may modulate brain aging by mediating complex sensory-motor functions.
Related JoVE Video
Dissecting molecular mechanisms in the living brain of dementia patients.
Acc. Chem. Res.
PUBLISHED: 03-14-2009
Show Abstract
Hide Abstract
Understanding the molecular mechanisms associated with the development of dementia is essential for designing successful interventions. Dementia, like cancer and cardiovascular disease, requires early detection to potentially arrest or prevent further disease progression. By the time a neurologist begins to manage clinical symptoms, the disease has often damaged the brain significantly. Because successful treatment is the logical goal, detecting the disease when brain damage is still limited is of the essence. The role of chemistry in this discovery process is critical. With the advent of molecular imaging, the understanding of molecular mechanisms in human neurodegenerative diseases has exploded. Traditionally, knowledge of enzyme and neurotransmitter function in humans has been extrapolated from animal studies, but now we can acquire data directly from both healthy and diseased human subjects. In this Account, we describe the use of molecular imaging probes to elucidate the biochemical and cellular bases of dementia (e.g., Alzheimers disease) and the application of these discoveries to the design of successful therapeutic interventions. Molecular imaging permits observation and evaluation of the basic molecular mechanisms of disease progression in the living brains of patients. 2-Deoxy-2-[(18)F]fluoro-d-glucose is used to assess the effect of Alzheimers disease progression on neuronal circuits projecting from and to the temporal lobe (one of the earliest metabolic signs of the disease). Recently, we have developed imaging probes for detection of amyloid neuropathology (both tau and beta-amyloid peptide deposits) and neuronal losses. These probes allow us to visualize the development of pathology in the living brain of dementia patients and its consequences, such as losses of critical neurons associated with memory deficits and other neuropsychiatric impairments. Because inflammatory processes are tightly connected to the brain degenerative processes, inflammation is now emerging as an important target for new molecular imaging probes. The combination of molecular probes targeting various processes of dementia is a useful tool for detailed monitoring of disease mechanism, progression, and diagnosis, as well as for the development of rational strategies for promising therapeutic interventions.
Related JoVE Video
Digital filtering and model updating methods for improving the robustness of near-infrared multivariate calibrations.
Appl Spectrosc
PUBLISHED: 02-14-2009
Show Abstract
Hide Abstract
Fourier transform near-infrared (NIR) transmission spectra are used for quantitative analysis of glucose for 17 sets of prediction data sampled as much as six months outside the timeframe of the corresponding calibration data. Aqueous samples containing physiological levels of glucose in a matrix of bovine serum albumin and triacetin are used to simulate clinical samples such as blood plasma. Background spectra of a single analyte-free matrix sample acquired during the instrumental warm-up period on the prediction day are used for calibration updating and for determining the optimal frequency response of a preprocessing infinite impulse response time-domain digital filter. By tuning the filter and the calibration model to the specific instrumental response associated with the prediction day, the calibration model is given enhanced ability to operate over time. This methodology is demonstrated in conjunction with partial least squares calibration models built with a spectral range of 4700-4300 cm(-1). By using a subset of the background spectra to evaluate the prediction performance of the updated model, projections can be made regarding the success of subsequent glucose predictions. If a threshold standard error of prediction (SEP) of 1.5 mM is used to establish successful model performance with the glucose samples, the corresponding threshold for the SEP of the background spectra is found to be 1.3 mM. For calibration updating in conjunction with digital filtering, SEP values of all 17 prediction sets collected over 3-178 days displaced from the calibration data are below 1.5 mM. In addition, the diagnostic based on the background spectra correctly assesses the prediction performance in 16 of the 17 cases.
Related JoVE Video
Multivariate calibration with basis functions derived from optical filters.
Anal. Chem.
PUBLISHED: 02-12-2009
Show Abstract
Hide Abstract
Multivariate calibration models are constructed through the use of Gaussian basis functions to extract relevant information from single-beam spectral data. These basis functions are related by analogy to optical filters and offer a pathway to the direct implementation of the calibration model in the spectrometer hardware. The basis functions are determined by use of a numerical optimization procedure employing genetic algorithms. This calibration methodology is demonstrated through the development of quantitative models in near-infrared spectroscopy. Calibrations are developed for the determination of physiological levels of glucose in two synthetic biological matrixes, and the resulting models are tested by application to external prediction data collected as much as 4 months outside the time frame of the calibration data used to compute the models. The calibrations developed with the Gaussian basis functions are compared to conventional calibration models computed with partial least-squares (PLS) regression. For both data sets, the models based on the Gaussian functions are observed to outperform the PLS models, particularly with respect to calibration stability over time.
Related JoVE Video
Your brain on Google: patterns of cerebral activation during internet searching.
Am J Geriatr Psychiatry
PUBLISHED: 01-22-2009
Show Abstract
Hide Abstract
Previous research suggests that engaging in mentally stimulating tasks may improve brain health and cognitive abilities. Using computer search engines to find information on the Internet has become a frequent daily activity of people at any age, including middle-aged and older adults. As a preliminary means of exploring the possible influence of Internet experience on brain activation patterns, the authors performed functional magnetic resonance imaging (MRI) of the brain in older persons during search engine use and explored whether prior search engine experience was associated with the pattern of brain activation during Internet use.
Related JoVE Video
Spectral simulation protocol for extending the lifetime of near-infrared multivariate calibrations.
Anal. Chem.
PUBLISHED: 01-10-2009
Show Abstract
Hide Abstract
Multivariate calibration models based on synthetic single-beam near-infrared spectra are used to demonstrate the ability to maintain viable calibrations over extended time periods. Glucose is studied over the physiological concentration range of 1-30 mM in a buffered aqueous matrix containing varying levels of alanine, ascorbate, lactate, urea, and triacetin. By employing a set of 25 test samples measured 23 times over a period of 325 days, partial least-squares (PLS) calibrations based on synthetic spectra are observed to outperform conventional calibrations that use a set of 64 measured calibration samples. The key to the success of this approach is the use of a set of spectra of phosphate buffer collected on each prediction day to construct synthetic calibration spectra that are specific to that day. This allows the incorporation into the calibration model of nonanalyte spectral variance that is unique to a particular day. In this way, the adverse effects of instrumental drift or other sources of spectral variance on prediction performance can be minimized. Through the application of this methodology, values of the standard error of prediction (SEP) for glucose concentration are maintained to a range of 0.50-0.95 mM and an average of 0.68 mM over the 325 days of the experiment. These results are significantly better than those obtained with conventional models based on measured calibration samples. Over the same time period, a PLS model based on measured calibration spectra in absorbance units produced values of SEP that ranged from 0.41 to 2.02 mM and an average of 1.23 mM.
Related JoVE Video
Influence of cognitive status, age, and APOE-4 genetic risk on brain FDDNP positron-emission tomography imaging in persons without dementia.
Arch. Gen. Psychiatry
PUBLISHED: 01-07-2009
Show Abstract
Hide Abstract
Amyloid senile plaques and tau neurofibrillary tangles are neuropathological hallmarks of Alzheimer disease that accumulate in the brains of people without dementia years before they develop dementia. Positron emission tomography (PET) scans after intravenous injections of 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP), which binds to plaques and tangles in vitro, demonstrate increased cerebral binding in patients with Alzheimer disease compared with cognitively intact controls. Here we investigated whether known risk factors for Alzheimer disease and dementia are associated with FDDNP-PET binding.
Related JoVE Video
Differential diagnoses and assessment of depression in elderly patients.
J Clin Psychiatry
PUBLISHED: 01-02-2009
Show Abstract
Hide Abstract
Depression in the elderly contributes to decreased quality of life and increased mortality from both suicide and medical illnesses, yet it remains underdiagnosed and undertreated in these patients. Physicians should be aware of the varying presentations of depression in older adults and differentiate late-life depression from other psychiatric diagnoses. Thorough medical and cognitive assessments are necessary to determine whether late-life depression is due to underlying medical causes and neurologic diagnoses such as Alzheimers disease or dementia. Depression rating scales, cognitive screening instruments, and structural and functional neuroimaging studies may be implemented as the situation requires. Greater recognition and more aggressive treatment of depression in older patients are needed.
Related JoVE Video
Advances in cardiac SPECT and PET imaging: overcoming the challenges to reduce radiation exposure and improve accuracy.
Can J Cardiol
Show Abstract
Hide Abstract
Nuclear cardiology came of age in the 1970s and subsequently has expanded so that more than 9 million single-photon emission computed tomography (SPECT) studies are performed annually in North America. Coronary artery disease management has demanded a reliable technique that will detect, risk stratify, and assist with revascularization decisions. Using cardiac SPECT and positron-emission tomography (PET), researchers and clinicians have sought to achieve excellence in coronary artery disease diagnosis and risk stratification, and strive to achieve higher standards in these areas. Developments in other cardiac imaging modalities, however, such as cardiac computed tomography, cardiac magnetic resonance, and echocardiography, have raised expectations in terms of diagnostic accuracy and achieving high quality images with little or no ionizing radiation exposure. The challenge facing nuclear cardiology as it embarks upon a fifth decade of clinical use is whether high quality images can be obtained at lower radiation exposures. In this review we consider current practice in SPECT and PET perfusion imaging. We discuss emerging advances in techniques, technologies, and radiotracers that focus specifically on improvements in image quality that enhance diagnostic accuracy while reducing radiation exposure. We provide a perspective as to the future roles of cardiac SPECT and PET in ischemic heart disease, and consider emerging novel applications beyond perfusion imaging. Although for a number of years nuclear cardiology has shone brightly as a leading light for the imaging of ischemic heart disease, its half-life has not yet been reached. Instead, even with the pressure to reduce radiation exposure, the future continues to look bright for cardiac SPECT and PET.
Related JoVE Video
Repeat expansions in the C9ORF72 gene contribute to Alzheimers disease in Caucasians.
Neurobiol. Aging
Show Abstract
Hide Abstract
Recently, a hexanucleotide repeat expansion in the C9ORF72 gene has been identified to account for a significant portion of Caucasian families affected by frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Given the clinical overlap of FTD with Alzheimers disease (AD), we hypothesized that C9ORF72 expansions might contribute to AD. In Caucasians, we found C9ORF72 expansions in the pathogenic range of FTD/ALS (>30 repeats) at a proportion of 0.76% in AD cases versus 0 in control subjects (p = 3.3E-03; 1182 cases, 1039 controls). In contrast, no large expansions were detected in individuals of African American ethnicity (291 cases, 620 controls). However, in the range of normal variation of C9ORF72 expansions (0-23 repeat copies), we detected significant differences in distribution and mean repeat counts between Caucasians and African Americans. Clinical and pathological re-evaluation of identified C9ORF72 expansion carriers revealed 9 clinical and/or autopsy confirmed AD and 2 FTD final diagnoses. Thus, our results support the notion that large C9ORF72 expansions lead to a phenotypic spectrum of neurodegenerative disease including AD.
Related JoVE Video
Anxiety and verbal memory performance in APOE-4 carriers and noncarriers aged 50 years and above.
Aging health
Show Abstract
Hide Abstract
AIMS: The current study sought to explore the relationship between state and trait anxiety and delayed verbal memory performance in APOE-4 carriers and noncarriers who were aged 50 years and above. MATERIALS #ENTITYSTARTX00026; METHODS: The study was a retrospective analysis of 267 participants aged 50 years and above who had completed genetic testing for APOE status, the State-Trait Anxiety Inventory, and a comprehensive neuropsychological battery that included three delayed verbal memory measures (Wechsler Memory Scale - 3rd Edition, Logical Memory and Verbal Pairs subtests and the Buschke Selective Reminding Test). RESULTS: An inverse relationship was found between state anxiety and delayed verbal memory performance. No difference in level of anxiety was found between APOE-4 carriers versus noncarriers. CONCLUSION: State anxiety, but not trait anxiety, was found to have an inverse relationship with delayed verbal memory performance. For example, as self-reported state anxiety increased, delayed verbal memory scores decreased. This relationship did not appear to be influenced by the presence or absence of the APOE-4 allele.
Related JoVE Video
Prediction of cognitive decline based on hemispheric cortical surface maps of FDDNP PET.
Neuroimage
Show Abstract
Hide Abstract
A cross-sectional study to establish whether a subjects cognitive state can be predicted based on regional values obtained from brain cortical maps of FDDNP Distribution Volume Ratio (DVR), which shows the pattern of beta amyloid and neurofibrillary binding, along with those of early summed FDDNP PET images (reflecting the pattern of perfusion) was performed.
Related JoVE Video
Family history and APOE-4 genetic risk in Alzheimers disease.
Neuropsychol Rev
Show Abstract
Hide Abstract
Identifying risk factors for Alzheimers disease, such as carrying the APOE-4 allele, and understanding their contributions to disease pathophysiology or clinical presentation is critical for establishing and improving diagnostic and therapeutic strategies. A first-degree family history of Alzheimers disease represents a composite risk factor, which reflects the influence of known and unknown susceptibility genes and perhaps non-genetic risks. There is emerging evidence that investigating family history risk associated effects may contribute to advances in Alzheimers disease research and ultimately clinical practice.
Related JoVE Video
Sphingosine-1-phosphate-induced release of TIMP-2 from vascular smooth muscle cells inhibits angiogenesis.
J. Cell. Sci.
Show Abstract
Hide Abstract
Following myocardial infarction, angiogenesis occurs as a result of thrombus formation, which permits reperfusion of damaged myocardium. Sphingosine 1-phosphate (S1P) is a naturally occurring lipid mediator released from platelets and is found in high concentrations at sites of thrombosis. S1P might therefore be involved in regulating angiogenesis following myocardial infarction and might influence reperfusion. The aims of this study were to determine the effects of S1P in human coronary arterial cell angiogenesis and delineate the subsequent mechanisms. An in vitro model of angiogenesis was developed using a co-culture of human coronary artery endothelial cells, human coronary smooth muscle cells and human fibroblasts. In this model, S1P inhibited angiogenesis and this was dependent on the presence of smooth muscle cells. The mechanism of the inhibitory effect was through S1P-induced release of a soluble mediator from smooth muscle cells. This mediator was identified as tissue inhibitor of metalloproteinase-2 (TIMP-2). Release of TIMP-2 was dependent on S1P-induced activation of Rho kinase and directly contributed to incomplete formation of endothelial cell adherens junctions. This was observed as a diffuse localisation of VE-cadherin, leading to decreased tubulogenesis. A similar inhibitory response to S1P was demonstrated in an ex vivo human arterial model of angiogenesis. In summary, S1P-induced inhibition of angiogenesis in human artery endothelial cells is mediated by TIMP-2 from vascular smooth muscle cells. This reduces the integrity of intercellular junctions between nascent endothelial cells. S1P might therefore inhibit the angiogenic response following myocardial infarction.
Related JoVE Video
Self-reported memory impairment and brain PET of amyloid and tau in middle-aged and older adults without dementia.
Int Psychogeriatr
Show Abstract
Hide Abstract
Whether perceived changes in memory parallel changes in brain pathology is uncertain. Positron emission tomography (PET) scans using 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile (FDDNP) can measure levels of amyloid plaques and tau neurofibrillary tangles in vivo. Here we investigate whether degree of self-reported memory impairment is associated with FDDNP-PET binding levels in persons without dementia.
Related JoVE Video
Prediction of cognitive decline by positron emission tomography of brain amyloid and tau.
Arch. Neurol.
Show Abstract
Hide Abstract
To determine whether 2-(1-{6-[(2-fluorine 18-labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([(18)F]FDDNP) brain regional values in individuals without dementia predict and correlate with future cognitive change.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.