lesion-explorer-video-guided-standardized-protocol-for-accurate

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly

Obtaining in vivo human brain tissue volumetrics from MRI is often complicated by various technical and biological issues. These challenges are ...

Singhal et al. [Psychophysiology 39 (2002) 236] reported that the amplitude of the late negative difference (Nd) and P300 components, generated by a dichotic listening task, were decreased in parallel by a simultaneously performed visual flying task. In contrast, early Nd was unaffected. To investigate the role of covert spatial attention in this pattern of results, we substituted Posner's attention switching paradigm for the flying task. Fourteen subjects performed the dichotic listening and attention tasks alone and in combination. The results showed that only the invalid/valid condition of the Posner task reduced the amplitude of the late Nd, while the early Nd was unaffected. Contrary to the earlier study, P300 dissociated from the late Nd and its amplitude decreased in both the invalid/valid and neutral conditions of the Posner task. We conclude that the late Nd is sensitive to some aspect of attention switching and that the late Nd and P300 share sensitivity to an amodal system to which the early Nd is insensitive. Within this system, the late Nd is differentiated from P300 by its narrow sensitivity to attentional processing whereas P300 is sensitive to a broader range of processing. These similarities and differences are explained in the context of a modified version of Kok's model [Psychophysiology 38 (2001) 557] of the determinants of P300 amplitude.

Influence of a visual spatial attention task on auditory early and late Nd and P300.

The representation of autobiographical memory is distributed over a network of brain structures, with the medial temporal lobe (MTL) at its epicenter. Some believe that, over time, all memories become independent of their MTL component ("consolidation theories"). Others have suggested that this is true only of semantic memory, while episodic aspects of autobiographical memories are dependent on the MTL for as long as they exist, such as multiple trace theory (MTT). In the present study, the volumes of 28 brain regions, including the MTL, and their relation to autobiographical memory were investigated in a group of patients with Alzheimer's disease with varying degrees of retrograde memory loss as assessed by the Autobiographical Memory Interview (AMI). We used the multivariate analysis method of partial least squares (PLS) to assess patterns of atrophy that can lead to retrograde amnesia. We found that different aspects of autobiographical memory were associated with different patterns of tissue loss. Personal semantics were related to a pattern of bilateral anterior and posterior lateral temporal cortex degeneration, more pronounced on the left, as well as right frontal degeneration. Autobiographical event memory ("episodic") was associated with combined atrophy in bilateral MTL and anterior lateral temporal neocortex, more pronounced on the right. This pattern was invariant for memories from childhood, early adulthood, and recent memories, in line with the predictions of MTT, suggesting that MTL tissue is crucial for retrieval of episodic memories regardless of their age.

Retrieval of autobiographical memory in Alzheimer's disease: relation to volumes of medial temporal lobe and other structures.

Nitric oxide (NO) is an important reactive molecule in many organisms. A mitochondrial nitric oxide synthase has been described; however, the role of NO in this organelle is not yet fully clear. We tested the effect of intramitochondrial NO on various functions from spontaneously hypertensive rats (SHR) and their normotensive genetic control, Wistar-Kyoto (WKY) rats. While the stimulation of intramitochondrial NOS increased calcium- and phosphate-induced permeability transition pore opening, its inhibition partially prevented it, without affecting membrane potential. Matrix free calcium and the pH decreased with NOS inhibition. Basal [NO] was lower in SHR than in WKY. Our data suggest that intramitochondrial NO plays an important role in mitochondrial regulation during hypertension.

Role of intramitochondrial nitric oxide in rat heart and kidney during hypertension.

Stickstoffmonoxid (NO) ist ein wichtiger reaktives Molek&uuml;l in vielen Organismen. Ein mitochondriales Stickstoffmonoxid-Synthase ist beschrieben worden; die Rolle der Nr. in diesem Organell ist jedoch noch nicht ganz klar. Wir testeten die Wirkung von Intramitochondrial nicht auf verschiedene Funktionen von spontan Hypertensive Ratten (SHR) und ihre normotensive genetische Kontrolle, Ratten Wistar-Kyoto (WKY). W&auml;hrend die Stimulation der Intramitochondrial NOS Kalzium und Phosphat-induzierte Permeabilit&auml;t &Uuml;bergang Pore Er&ouml;ffnung gestiegen sind, verhindert seine Hemmung, teilweise ohne Membran potenzielle. Matrix freie Calcium und pH sank mit NOS-Hemmung. Basale [NO] lagen in SHR als in WKY. Unsere Daten legen nahe, dass diese Intramitochondrial nicht spielt eine wichtige Rolle in mitochondrialen Verordnung w&auml;hrend der Hypertonie.

Die Rolle der Intramitochondrial Stickstoffmonoxid in Ratte Herz und Niere bei Bluthochdruck.

As imaging centers produce higher resolution research scans, the number of man-hours required to process regional data has become a major concern. Comparison of automated vs. manual methodology has not been reported for functional imaging. We explored validation of using automation to delineate regions of interest on positron emission tomography (PET) scans. The purpose of this study was to ascertain improvements in image processing time and reproducibility of a semi-automated brain region extraction (SABRE) method over manual delineation of regions of interest (ROIs).

Comparison of manual and semi-automated delineation of regions of interest for radioligand PET imaging analysis.

MRI-based quantification of gray and white matter volume is common in studies involving elderly patient populations. The aim of the present study was to describe the effects of not accounting for subcortical white matter hyperintensities (WMH) on tissue volumes in Alzheimer Disease patients with varying degrees of WMH (mild: n=19, moderate: n=22, severe: n=18).

Misclassified tissue volumes in Alzheimer disease patients with white matter hyperintensities: importance of lesion segmentation procedures for volumetric analysis.

MRI-basierte Quantifizierung der grauen und wei&szlig;en Angelegenheit Volumen ist h&auml;ufig in Studien mit &auml;ltere Patientenpopulationen. Das Ziel der vorliegenden Studie war es, die Auswirkungen der subkortikalen wei&szlig;en Substanz Hyperintensities (WMH) nicht auf Gewebe-Volumes bei Alzheimer-Krankheit Patienten mit unterschiedlichem WMH Bilanzierung zu beschreiben (mild: n = 19, moderate: n = 22, schwere: n = 18).

Befund Gewebe Volumen bei Alzheimer Patienten mit wei&szlig;en Substanz Hyperintensities: Bedeutung der L&auml;sion Segmentierung Verfahren f&uuml;r volumetrische Analyse.

Depressive symptoms of varying severity are prevalent in up to 63% of Alzheimer disease (AD) patients and often result in greater cognitive decline and increased caregiver burden. The current study aimed to determine the neural correlates of depressive symptoms in a sample of AD patients.

Frontal lobe hypoperfusion and depressive symptoms in Alzheimer disease.

The clinical syndrome of the frontotemporal dementias (FTD) overlaps with frontal-subcortical circuit syndromes. We explored the extent to which subcortical atrophy on structural magnetic resonance imaging may indicate a subcortical contribution to the progression of FTD.

Magnetic resonance imaging in frontotemporal dementia shows subcortical atrophy.

Normal aging leads to frontocortical atrophy. The degree to which this complicates the use of frontotemporal atrophy as a diagnostic criterion for the frontotemporal dementias (FTDs) has not been reported. The present case-control study compared frontotemporal volumes delineated with semi-automatic brain region extraction [n=30 controls vs. 16 behavioral variant FTD (bvFTD) vs. 14 primary progressive aphasia]. Logistic regression identified those regions least helpful for distinguishing bvFTD and primary progressive aphasia from controls. Linear regression tested the correlation of duration of illness to atrophy severity. The control group showed high variance in volumes. Controls had right frontal lobe volumes that overlapped considerably with bvFTD volumes, but, as anticipated, the left anterior temporal volumes of interest showed 91% accuracy in distinguishing the aphasic subgroup from controls. Left-sided and not right-sided atrophy in the medial middle frontal region distinguished the bvFTD group from controls. The relegation of structural imaging to a supportive criterion for diagnosis is reasonable in the context of the range of atrophy due to normal aging. While volumetry identified left-sided atrophy as useful for identifying FTD cases, future studies should determine whether clinicians could make these distinctions on viewing routine diagnostic magnetic resonance imaging scans.

Overlap in frontotemporal atrophy between normal aging and patients with frontotemporal dementias.

To determine whether basal ganglia atrophy, known to be associated with apathy in nondementia populations, was associated with presence of apathy in patients with frontotemporal dementia (FTD).

Apathy is not associated with basal ganglia atrophy in frontotemporal dementia.

Lesion Explorer (LE) is a reliable and comprehensive MRI-derived tissue segmentation and brain region parcellation processing pipeline for obtaining intracranial tissue and subcortical hyperintensity (SH) volumetrics. The processing pipeline segments: gray (GM) and white matter (WM); sulcal (sCSF) and ventricular cerebrospinal fluid (vCSF); periventricular (pvSH) and deep white subcortical hyperintensities (dwSH); and cystic fluid filled lacunar-like infarcts (Lacunar); into 26 regions of interest. A short-term scan-rescan reliability test was performed on 20 healthy volunteers: 10 older (mean = 77.7 years, SD = 11.1) and 10 younger (mean = 29.4 years, SD = 7.1). Each participant was scanned twice with an average interscan interval of 15.4 days (range: 29 min-50 days). Results suggest low technique-related error as indicated by excellent intraclass correlation coefficient (ICC) results, with ICCs above 0.90 (p < 0.05) for GM, WM, and CSF, in all 26 regions of interest (13 per hemisphere). Ventricular and lesion sub-type (pvSH, dwSH, and Lacunar) volumes also showed high scan-rescan reliability (dwSH = 0.9998, pvSH = 0.9998, Lacunar = 0.9859, p < 0.01). As indicated by the results of this short-term scan-rescan study, the LE structural MRI processing pipeline can be applied for longitudinal volumetric analyses with confidence.

A short-term scan-rescan reliability test measuring brain tissue and subcortical hyperintensity volumetrics obtained using the lesion explorer structural MRI processing pipeline.

The approach to and management of the athlete with concussion can be a challenging endeavor to physicians who care for athletes who have suffered a head injury--this group includes family physicians, pediatricians, internists, emergency medicine physicians, primary sports medicine physicians, orthopedic surgeons, neurologists, and neurosurgeons. Sometimes questions regarding the need for neurologic, psychological, or radiographic imaging can make the decision for return to play unclear. New legislation will undoubtedly increase physician visits for these athletes to return to play. Thus, the goal of this article is to review the latest guidelines regarding concussion management to help all physicians who care for athletes do so appropriately.

Management of the athlete with concussion.

We studied behavioral variant frontotemporal dementia (bvFTD) using object alternation (OA) as a novel probe of cognition. This task was adopted from animal models and is sensitive to ventrolateral-orbitofrontal and medial frontal function in humans. OA was administered to bvFTD patients, normal controls, and a dementia control group with Alzheimer disease (AD). Two other frontal lobe measures adopted from animal models were administered: delayed response (DR) and delayed alternation (DA). Brain volumes were measured using the semiautomatic brain region extraction method. Compared with the normal controls, bvFTD patients were significantly impaired on OA and DR. For OA and DR, sensitivities and specificities were 100% and 51.5% (cutoff=22.5 errors) and 9.5% and 98% (cutoff=1.5 errors), respectively. Negative predictive value (NPV) for OA was 100% at all prevalence rates. Comparing AD with bvFTD, there were no significant differences on OA, DR, or DA. Nevertheless, positive predictive value (PPV) and NPV were good at all prevalence rates for OA (cutoff=36.5 errors) and DA (cutoff=6 errors); PPV was good for DR (cutoff=9 errors). Error scores above cutoffs favored diagnosis of AD. Performance on OA was significantly related to medial frontal gray matter atrophy. OA, together with DR and DA, may facilitate assessment of bvFTD as a novel probe of medial frontal function.

Object alternation: a novel probe of medial frontal function in frontotemporal dementia.

We previously identified SMIP004 (N-(4-butyl-2-methyl-phenyl) acetamide) as a novel inducer of cancer-cell selective apoptosis of human prostate cancer cells. SMIP004 decreased the levels of positive cell cycle regulators, upregulated cyclin-dependent kinase inhibitors, and resulted in G1 arrest, inhibition of colony formation in soft agar, and cell death. However, the mechanism of SMIP004-induced cancer cell selective apoptosis remained unknown. Here, we used chemical genomic and proteomic profiling to unravel a SMIP004-induced pro-apoptotic pathway, which initiates with disruption of mitochondrial respiration leading to oxidative stress. This, in turn, activates two pathways, one eliciting cell cycle arrest by rapidly targeting cyclin D1 for proteasomal degradation and driving the transcriptional downregulation of the androgen receptor, and a second pathway that activates pro-apoptotic signaling through MAPK activation downstream of the unfolded protein response (UPR). SMIP004 potently inhibits the growth of prostate and breast cancer xenografts in mice. Our data suggest that SMIP004, by inducing mitochondrial ROS formation, targets specific sensitivities of prostate cancer cells to redox and bioenergetic imbalances that can be exploited in cancer therapy.

Article	Year
Influence of a visual spatial attention task on auditory early and late Nd and P300. Biological psychology\| PubMed ID: 15450692	2005
Retrieval of autobiographical memory in Alzheimer's disease: relation to volumes of medial temporal lobe and other structures. Hippocampus\| PubMed ID: 15884035	2005
Role of intramitochondrial nitric oxide in rat heart and kidney during hypertension. Mitochondrion\| PubMed ID: 16120294	2002
Comparison of manual and semi-automated delineation of regions of interest for radioligand PET imaging analysis. BMC nuclear medicine\| PubMed ID: 17261193	2007
Misclassified tissue volumes in Alzheimer disease patients with white matter hyperintensities: importance of lesion segmentation procedures for volumetric analysis. Stroke; a journal of cerebral circulation\| PubMed ID: 18323507	2008
Frontal lobe hypoperfusion and depressive symptoms in Alzheimer disease. Journal of psychiatry & neuroscience : JPN\| PubMed ID: 18592038	2008
Magnetic resonance imaging in frontotemporal dementia shows subcortical atrophy. Dementia and geriatric cognitive disorders\| PubMed ID: 18617738	2008
Overlap in frontotemporal atrophy between normal aging and patients with frontotemporal dementias. Alzheimer disease and associated disorders\| PubMed ID: 18695590	2008
Apathy is not associated with basal ganglia atrophy in frontotemporal dementia. The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry\| PubMed ID: 19700954	2009
A short-term scan-rescan reliability test measuring brain tissue and subcortical hyperintensity volumetrics obtained using the lesion explorer structural MRI processing pipeline. Brain topography\| PubMed ID: 22562092	2013
Management of the athlete with concussion. The Permanente journal\| PubMed ID: 22745617	2012
Object alternation: a novel probe of medial frontal function in frontotemporal dementia. Alzheimer disease and associated disorders\| PubMed ID: 23604006	2013
Small molecule-induced mitochondrial disruption directs prostate cancer inhibition via UPR signaling. Oncotarget\| PubMed ID: 23902736	2013

Joel Ramirez

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