Functional Caudate Imaging in Symptomatic Huntington's Disease: Positron Emission Tomography Versus SinglePhoton Emission Computed Tomography

Functional neuroimaging with positron emission tomography previously demonstrated reduced caudate glucose metabolism in virtually all symptomatic patients with Huntington's disease (HD) Single-photon emission computed tomography studies of brain blood flow also have shown caudate abnormalities in patients with HD. The present study compared these two functional imaging modalities in 6 patients with HD who had been symptomatic for fewer than 5 years. All patients had significantly impaired caudate-thalamus and caudate-whole-slice glucose metabolism ratios as measured by positron emission tomography. However, only 3 had clearly abnormal caudate-thalamus activity ratios and 2 had clearly abnormal caudate-whole-slice ratios on single-photon emission computed tomography. These findings indicate that single-photon emission computed tomography imaging of caudate blood flow is a less sensitive indicator of caudate dysfunction in early HD than is positron emission tomography imaging of caudate glucose metabol1sm.     

Contribution of neuroimaging in the diagnosis of Alzheimer's disease and other dementias

This paper reviews the use of neuroimaging in the diagnosis of dementia, especially Alzheimer's disease. Computed tomography is still used to determine reversible causes of dementia; however, without clinical symptoms these causes are hard to find and computed tomography scanning is only cost-effective in a defined group of patients. Using magnetic resonance imaging, atrophy of the medial temporal lobe can be assessed volumetrically and visually, with a high correlation between the two methods. Medial temporal lobe atrophy is highly predictive of Alzheimer's disease, and correlates with neuropsychological performance and postmortem histologically measured volume. Cerebral volume changes over time seem to differentiate Alzheimer's disease and mild cognitive impairment progressing to Alzheimer's disease from controls with high accuracy. Studies of the corpus callosum in dementia indicate a cortico-cortical disconnection caused by atrophy. Of the new techniques, functional magnetic resonance imaging seems the most promising. This technique can possibly play a role in predicting Alzheimer's disease in patients with mild cognitive impairment. The use of single-photon emission computed tomography and positron emission tomography in (early) differential diagnoses seems limited. Lower regional cerebral blood flow is related to the severity of dementia and survival. Iodine-123 iodobenzamide single-photon emission computed tomography in dementia with Lewy bodies seems promising. Current and future positron emission tomography studies concentrate on memory function and receptor imaging. The focus in neuroimaging, especially magnetic resonance imaging, has shifted to early diagnosis and monitoring of the disease course, with a special interest in predicting dementia in patients with mild cognitive impairment.     

Slowly progressive aphasia without generalized dementia: studies with positron emission tomography

Slowly progressive aphasia without generalized dementia is a degenerative syndrome selectively affecting dominant hemisphere language areas. We report changes in regional glucose metabolism measured by positron emission tomography in two patients with this condition. Striking abnormalities of glucose utilization in the left cerebral cortex were demonstrated in both patients. The findings of other neurodiagnostic studies were relatively unremarkable. The first patient had a 3-year history of progressive anomia and impaired auditory verbal recall. An electroencephalogram was normal, and computed tomography showed mild left perisylvian atrophy. Positron emission tomography revealed profound hypometabolism in the left temporal regions. The second patient also had a 3-year history of progressive anomia. Electroencephalography, computed tomography, and magnetic resonance imaging scans were normal. Positron emission tomography showed a major reduction in left parietal glucose utilization, with a lesser decrement in left temporal metabolism. Neither patient demonstrated significant contralateral or global abnormalities such as those reported in positron emission tomographic studies of Alzheimer's disease with or without focal clinical features. These observations support the concept of adult-onset progressive aphasia without dementia as a clinical syndrome distinct from Alzheimer's disease.     

Disorders of glucose metabolism in Pick's disease

A clinically diagnosed case of advanced Pick's disease served to illustrate that positron emission tomography is a sensitive method for diagnosing complex functional disturbances. Pick's disease can be differentiated against presenile dementia represented by Alzheimer's disease in that the pattern of reduced metabolism characteristic of Alzheimer's disease is different from that of Pick's disease where in accordance with the clinical syndrome the glucose metabolism in the frontal and temporobasal regions in reduced, involving also the structures of the hippocampus and an equally significant reduction of glucose metabolism in the caudate nucleus. Especially during the initial phase of the disease when structural changes are not yet evident or the clinical manifestation of the syndrome does not correlate with the degree of lobar atrophy seen in the computer tomogram or via magnetic resonance tomography, positron emission tomography can make differential diagnosis much easier.     

Assessing the machinery of mind: synapses in neuropsychiatric disorders

Neural connectivity in postmortem human brain can now be studied with the use of antibodies that react with synapse-enriched proteins. Using a range of antibody-based techniques, the authors observed abnormalities in connectivity in Alzheimer's disease, temporal lobe epilepsy, and schizophrenia. They also found disease-related differences in the individual protein markers affected and in the anatomical distribution of differences from controls. Molecular and cellular abnormalities in neural connectivity may underlie functional abnormalities observed in vivo using positron emission tomography or functional magnetic resonance imaging.     

Diffusion-weighted magnetic resonance imaging in probable Creutzfeldt-Jakob disease: a clinical-anatomic correlation.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare transmissible disease that typically causes a rapidly progressive dementia and leads to death in less than 1 year. Although a few anecdotal reports suggest that diffusion-weighted magnetic resonance imaging may help substantiate premortem diagnosis of CJD, detailed correlation between radiographic data and clinical, electrophysiologic, and metabolic parameters is not available. METHODS: Signal abnormalities on diffusion-weighted images in 3 consecutive patients with probable CJD were correlated with psychometric features, electroencephalographic findings, and functional images with either positron emission tomography or single photon emission computed tomography. RESULTS: Focality of abnormalities on diffusion-weighted image, not apparent on routine magnetic resonance images, correlated closely with clinical manifestations of CJD. The topographic distribution of signal abnormality on diffusion-weighted image corresponded with abnormal metabolism or perfusion on positron emission and single photon emission computed tomographic scans. In 2 cases, the laterality of diffusion abnormalities correlated with periodic sharp wave activity on electroencephalograms. CONCLUSION: These findings extend previous observations that suggested a diagnostic and localizing utility of diffusion-weighted imaging in CJD.     

Neurodegenerative movement disorders: the contribution of functional imaging

PURPOSE OF REVIEW: Functional imaging such as positron emission tomography and single-photon emission computed tomography provide sensitive tools to assess functional brain abnormalities associated with neurodegenerative disease. This review discusses recent findings in this field, with a focus on the detection and characterization of receptor binding and presynaptic dopamine changes in movement disorders. RECENT FINDINGS: The classical role of positron emission tomography and radioligands such as F-dopa and C-raclopride for investigating abnormalities of the presynaptic and postsynaptic dopaminergic system underlying Parkinson's disease, Parkinsonism and Huntington's disease has recently been made more powerful by the application of statistical mapping to localize changes in dopamine storage capacity and receptor binding across the whole brain at a voxel level. C-raclopride positron emission tomography provides an indirect marker of changes in levels of dopamine in the synaptic cleft. The application of this model in assessing dopamine changes in response to pharmacological, behavioural, motor task and magnetic stimulation in normal individuals and Parkinson's disease patients is reviewed. Recent studies using positron emission tomography and single-photon emission computed tomography to discriminate Parkinson's disease from essential tremor and Parkinsonism, the involvement of non-dopaminergic systems in Parkinson's disease and the role of cell transplantation in Parkinson's disease and Huntington's disease are also discussed. SUMMARY: Functional imaging techniques provide insight into the pathophysiology of Parkinson's disease, Parkinsonism, and Huntington's disease and the mechanisms of the progression of these diseases. They also play a role in assessing the efficacy of putative neuroprotective and restorative therapy, such as striatal infusions of neurotrophic factors and implants of fetal cells.     

Neuroimaging and psychopharmacology in the diagnosis and treatment of dementia

Contributions of noninvasive brain imaging technologies to the diagnosis of organic dementias with special reference to Alzheimer's disease are reviewed. Included among the different techniques are: a. computed tomography b. magnetic resonance imaging c. positron emission tomography. Biochemical hypotheses with possible relevance to the pathogenesis of Alzheimer's disease are presented and their therapeutic implications are discussed. Included among the different hypotheses are: a. interference with protein synthesis b. acetylcholine deficiency c. aluminum deposition. Present status of the pharmacotherapy of Alzheimer's disease is outlined.     

New Techniques in Magnetic Resonance and Epilepsy

Summary: Developments in magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT) have opened new opportunities for noninvasive brain investigation. Functional imaging methods involving noninvasive MRI and minimally invasive PET and SPECT are available that allow investigation of brain abnormality in intractable epilepsy patients. Noninvasive techniques enable the investigation of many aspects of the underlying neuropathologic basis of intractable seizures and of the relationship of functional abnormalities both to structural abnormalities and to the seizure focus. New MRI techniques demonstrate the structure of the brain in fine detail (especially the hippocampus), provide information about the underlying metabolism of brain regions, and demonstrate functional activity of the brain with high spatial and temporal resolution. The clinical impact of this noninvasive information cannot be overstated and these techniques provide indispensable information to neurologists specializing in epi-leptology. The proper use and interpretation of the findings provided by these new technologies will be a major challenge to epilepsy programs in the next few years.     

Neuroimaging of phakomatoses

The phakomatoses are congenital disorders manifesting with central nervous system and cutaneous abnormalities. The structures predominantly affected are those of ectodermal origin, including the skin, nervous system, and eyes. The 4 most common phakomatoses are neurofibromatosis (types 1 and 2), tuberous sclerosis, Sturge-Weber disease, and von Hippel-Lindau disease. Imaging of the brain and spine in these disorders plays an important role in diagnosis, as well as determining the extent of involvement and guiding surgical interventions. This article reviews the application of x-ray computed tomography and magnetic resonance imaging to these disorders, as well as that of newer, "functional" imaging techniques such as positron emission tomography, magnetic resonance perfusion imaging, and spectroscopy.     

Brain imaging in functional mental disorders

The application of brain imaging techniques to psychiatry is reviewed with respect to computerized tomography (CT), EEG topography, positron emission tomography (PET), and magnetic resonance imaging (MRI). While early computerized tomography studies have suggested structural abnormalities in schizophrenia, more recent studies have shown that most schizophrenics and patients with other disorders have normal CT scans. EEG topography and positron emission tomography have not been evaluated as fully as computerized tomography. However, preliminary studies indicate some functional abnormalities in schizophrenia and affective disorders compared to normal controls. Magnetic resonance imaging shows promise but has had only a limited application to date in psychiatry.     

Magnetic resonance and PET studies in the early diagnosis of Alzheimer's disease

The demographics of aging identify an immediate need for the early diagnosis and development of dementia prevention strategies. Recent neuropathological studies have pointed to the early involvement of the hippocampus and entorhinal cortex in the progression of Alzheimer's disease in the brain. In particular, these studies have implicated tau-related pathology as an important cause of neuronal death. In addition, there is a large body of evidence showing that beta-amyloid, which has a predilection for the neocortex, is also involved early in the course of the disease and may also have toxic effects on cells. In vivo cerebrospinal fluid studies have shown that markers for these brain changes have a diagnostic value for Alzheimer's disease and that some measures also provide diagnostic specificity for Alzheimer's disease. Structural and metabolic imaging studies demonstrate brain changes in impaired and at-risk individuals. While currently available magnetic resonance and positron emission tomography techniques are not by themselves specific for the pathologic features of Alzheimer's disease, there are patterns of change that have been useful for the early diagnosis. As such, both prediction and longitudinal imaging studies demonstrate a capacity to recognize abnormalities that relate to future Alzheimer's disease and most recently to future mild cognitive impairment. This review highlights cross-sectional, prediction, and longitudinal magnetic resonance and positron emission tomography imaging studies and attempts to put into perspective their utility for the early diagnosis of Alzheimer's disease, and for their utility to provide diagnostic specificity. It is concluded that there is considerable promise for an early and specific diagnosis for Alzheimer's disease by combining information from imaging and biomarker modalities.     

Congenital perisylvian syndrome: MRI and glucose PET correlations

Congenital perisylvian syndromes are late migration/cortical organization disorders associated with distinctive clinical and imaging features. The clinical, magnetic resonance imaging, and 2-deoxy-2-[18F] fluoro-D-glucose (FDG) positron emission tomography scan findings of six children (age range: 3.2-16.7 years; 5 males) with congenital perisylvian syndrome were evaluated. The patients presented with heterogenous neurologic impairments, depending upon the involved hemisphere and the extension of perisylvian malformation. Two manifested bilateral malformation and four manifested unilateral. The characteristic MRI finding consisting of a vertically oriented sylvian fissure continuous with the central and postcentral sulcus was associated with variable extension of bordering polymicrogyric cortex. The positron emission tomography scans of all patients revealed perisylvian metabolic abnormalities corresponding to the magnetic resonance imaging-defined abnormality. Variable extent of abnormal glucose metabolism was also observed in areas with normal magnetic resonance imaging features. All patients with unilateral magnetic resonance imaging abnormality exhibited abnormal glucose metabolism also in the contralateral side. The two patients with bilateral malformation had more extensive positron emission tomography abnormalities than the morphologic anomalies on MRI. Although MRI remains the diagnostic gold standard to detect the lesion, positron emission tomography scan is helpful to evaluate the full functional extension of the cortical anomaly, thereby contributing to the definition of the clinical severity of the syndrome.     

Imaging of Alzheimer''s Disease

Imaging is widely used in the evaluation of Alzheimer's disease (AD). In addition to imaging's traditional role of aiding in the exclusion of diseases that may be confused with AD, structural and functional imaging are being explored for potential use in the early detection of AD and as surrogate markers of treatment outcome. Volumetric measurements of the hippocampal and entorhinal regions using modern magnetic resonance imaging (MRI) and computed tomography are most widely studied in the discrimination of AD from nondemented aging and other dementias. Other imaging modalities include positron emission tomography and single-photon-emission computed tomography, which evaluate global and regional disturbances of blood flow and metabolism, and proton spectroscopy, which assesses neuronal degeneration and loss as marked by the presence of abnormal metabolites. Diffusion tensor and functional MRI, which examine white matter changes and brain-behavior relationships, are more recent techniques that contribute to the burgeoning application of imaging techniques to dementing illnesses and are notably improving our understanding of the pathophysiology of AD.     

Neuroimaging in Alzheimer's disease

This article reviews the recent neuroimaging studies of patients with Alzheimer's disease. The neuroimaging procedures discussed include computerized tomography, magnetic resonance imaging, positron emission tomography, and single-photon emission computerized tomography.     

Ictal SPECT in children with partial epilepsy due to focal cortical dysplasia

We studied the usefulness of ictal single-photon emission computed tomography in the presurgical evaluation of children with partial epilepsy resulting from focal cortical dysplasia. Fifteen children, age 1-18 years, were identified with partial epilepsy caused by focal cortical dysplasia (confirmed by histology) who underwent subtraction ictal single-photon emission computed tomography during presurgical evaluation. All children later underwent surgery at the Cleveland Clinic Epilepsy Center between 1996 and 2000. The findings of ictal single-photon emission computed tomography and brain positron emission tomography were classified as localized when "localizing and concordant" with the surgical resection site, nonconcordant when "localizing but not concordant" with the surgical resection, or nonlocalized when "no well-localized region of ictal hyperperfusion was observed on the difference image". In 15 patients, age 1.5-18 years (median age 8 years), epilepsy was classified as frontal in 7, posterior temporal/occipital in 3, temporal in 2, multilobar in 2, and parietal in 1. Of 15 patients, preoperative magnetic resonance imaging revealed focal cortical dysplasia in 11, positron emission tomography was localized in 9, and ictal single-photon emission computed tomography was localized in 8 patients. In 4 patients with normal magnetic resonance imaging but scalp electroencephalographic findings of partial epilepsy, ictal single-photon emission computed tomography and positron emission tomography were localized in 3 each. Fourteen patients were monitored for 6-39 months (mean 20 months). Six of 7 patients (85%) with localized ictal single-photon emission computed tomography compared with 4 of 7 (57%) with nonconcordant/nonlocalized ictal single-photon emission computed tomography had no seizures at follow-up. In 4 patients with normal magnetic resonance imaging, 3 patients with localized ictal single-photon emission computed tomography were free of seizures compared with 1 with nonconcordant ictal single-photon emission computed tomography who continued to have seizures. Ictal single-photon emission computed tomography is a useful adjunctive test in presurgical evaluation of children with refractory partial epilepsy due to focal cortical dysplasia, especially when brain magnetic resonance imaging is normal.     

Neuroimaging as a diagnostic tool in dementia with Lewy bodies

Due to similar presenting symptoms, many physicians find it difficult to distinguish cases of dementia with Lewy bodies (DLB) from Alzheimer's disease or Parkinson's disease with dementia. The pathologic diagnosis of DLB has improved because of the discovery of probes for alpha-synuclein, a protein found in Lewy bodies. However, pathologic diagnosis can be employed postmortem only, and therefore diagnostic techniques that can be employed to guide patient management are still needed. Consensus criteria have been developed for establishing a clinical diagnosis of DLB, but they lack sensitivity. Therefore, a review of the recent literature was conducted to establish whether neuroimaging studies are useful diagnostic tools to help differentiate these syndromes. At least six types of tests can be used to image the brain of patients with dementia. Structural studies (x-ray, magnetic resonance imaging and computerized tomography) can disclose the presence of stroke sequelae and other lesions, whereas functional studies (magnetic resonance spectroscopy, positron emission tomography and single-photon emission computed tomography) can disclose metabolic and blood flow alterations that may be characteristic for different types of dementia. Although more formal studies are needed to confirm that these imaging techniques are reliable diagnostic tools for DLB and permit the establishment of guidelines for their use, neuroimaging techniques currently are being employed in practice to differentiate dementia types as a guide to treatment.     

Sensitivity and specificity of neuroimaging for the diagnosis of Alzheimer's disease

Alzheimer's disease (AD) is one of the most devastating and cosily disorders affecting the aging population. Structural imaging (computed tomography [CT] and magnetic resonance imaging [MRI]) and functional imaging (single photon emission computed tomography [SPECT] and positron emission tomography [PET]) have been evaluated for their roles in the imaqinq diagnosis of AD. We have reviewed the recent literature to determine the capabilities of these neuroimaging techniques in comparison to current standards of clinical diagnosis. Our results indicate that there is wide variability in the accuracy of clinical assessments, in contrast to a more limited ranqe of variability of the accuracy of neuroimaqinq measurements. These results suggest that neuroimaging may serve an adjunctive role in raising this lower bound of diagnostic accuracy. Furthermore, we suggest that neuroimaging should be considered: (I) when clinical expertise is insufficient; (il) as a complement to specific likelihood ratios; and (iii) in specific types of patients, for whom clinical evaluation is inappropriate or inadequate.     

Introduction to the special issue on psychiatry in Asia

Abstract

Neuroimaging studies in schizophrenia help clarify the neural substrates underlying the pathogenesis of this neuropsychiatric disorder. Contemporary brain imaging in schizophrenia is predominated by magnetic resonance imaging (MRI)-based research approaches. This review focuses on the various imaging studies from India and their relevance to the understanding of brain abnormalities in schizophrenia. The existing studies are predominantly comprised of structural MRI reports involving region-of-interest and voxel-based morphometry approaches, magnetic resonance spectroscopy and single-photon emission computed tomography/positron emission tomography (SPECT/PET) studies. Most of these studies are significant in that they have evaluated antipsychotic-naïve schizophrenia patients – a relatively difficult population to obtain in contemporary research. Findings of these studies offer robust support to the existence of significant brain abnormalities at very early stages of the disorder. In addition, theoretically relevant relationships between these brain abnormalities and developmental aberrations suggest possible neurodevelopmental basis for these brain deficits.     

Molecular brain imaging in the multimodality era

Multimodality molecular brain imaging encompasses in vivo visualization, evaluation, and measurement of cellular/molecular processes. Instrumentation and software developments over the past 30 years have fueled advancements in multimodality imaging platforms that enable acquisition of multiple complementary imaging outcomes by either combined sequential or simultaneous acquisition. This article provides a general overview of multimodality neuroimaging in the context of positron emission tomography as a molecular imaging tool and magnetic resonance imaging as a structural and functional imaging tool. Several image examples are provided and general challenges are discussed to exemplify complementary features of the modalities, as well as important strengths and weaknesses of combined assessments. Alzheimer's disease is highlighted, as this clinical area has been strongly impacted by multimodality neuroimaging findings that have improved understanding of the natural history of disease progression, early disease detection, and informed therapy evaluation.