Methods for detecting early signs of AIDS dementia complex in asymptomatic HIV-1-infected subjects.

OBJECTIVES: To determine the optimal diagnostic procedures for identifying early signs of AIDS dementia complex (ADC) in asymptomatic HIV-1-infected individuals, in order to prevent further cognitive function impairment by early treatment. DESIGN: Study patients had been referred electively and consecutively to hospital; all had been referred for the first time and gave informed consent. Inclusion criteria were (1) lack of history and/or symptoms of psychosis and neurological disorders; (2) lack of active viral, protozoan or fungal pathology; (3) abstinence from heroin and/or cocaine for at least 6 months before baseline evaluation. SETTINGS: Subjects were seen at the L. Spallanzani Hospital for Infectious Diseases, Rome, Italy between March 1989 and March 1991. PARTICIPANTS: Eighty-two asymptomatic HIV-1-infected subjects: 41 drug users, 27 homosexuals and 14 heterosexuals. MAIN OUTCOME MEASURES: All subjects were evaluated using Wechsler-Bellevue I, Benton C form and Bender tests. Thirty-nine subjects underwent single-photon emission computed tomography (SPECT) and 12 magnetic resonance imaging (MRI). The immunological status of each subject was determined. RESULTS: On psychometric testing, 23 out of the 82 (28%) asymptomatic subjects had a mental decay percentage (MD%) > or = 20%. Cerebral perfusion abnormalities were detected in 31 out of 39 (79.48%) subjects who underwent SPECT; MRI abnormalities were observed in seven out of 12 (58%) subjects. Twelve out of 23 subjects with MD% > or = 20, 15 out of 29 subjects with SPECT abnormalities and four out of seven patients with MRI abnormalities had total CD4+ lymphocyte counts > or = 500 x 10(6)/l. CONCLUSIONS: The high incidence of abnormal SPECT and of MD% > or = 20 in asymptomatic HIV-1-infected patients, and the lack of correlation between immunological status and degree of mental decay, SPECT and MRI abnormalities raise many questions about subclinical HIV-1 neurological disease.     

Role of radionuclide imaging for diagnosis of device and prosthetic valve infections

Cardiovascular implantable electronic device(CIED) infection and prosthetic valve endocarditis(PVE) remain a diagnostic challenge.Cardiac imaging plays an important role in the diagnosis and management of patients with CIED infection or PVE.Over the past few years,cardiac radionuclide imaging has gained a key role in the diagnosis of these patients,and in assessing the need for surgery,mainly in the most difficult cases.Both ~(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(~(18)F-FDG PET/CT) and radiolabelled white blood cell single-photon emission computed tomography/computed tomography(WBC SPECT/CT) have been studied in these situations.In their 2015 guidelines for the management of infective endocarditis,the European Society of Cardiology incorporated cardiac nuclear imaging as part of their diagnostic algorithm for PVE,but not CIED infection since the data were judged insufficient at the moment.This article reviews the actual knowledge and recent studies on the use of ~(18)F-FDG PET/CT and WBC SPECT/CT in the context of CIED infection and PVE,and describes the technical aspects of cardiac radionuclide imaging.It also discusses their accepted and potential indications for the diagnosis and management of CIED infection and PVE,the limitations of these tests,and potential areas of future research.     

Mechanisms of neuronal injury and death in HIV-1 associated dementia

Infection with the human immunodeficiency virus-1 (HIV-1) and acquired immunodeficiency syndrome (AIDS) remain a persistent and even growing health problem worldwide. Besides its detrimental systemic effects on the immune system, HIV-1 seems to enter the brain very soon after peripheral infection and can induce severe and debilitating neurological problems that include behavioral abnormalities, motor dysfunction and frank dementia. Infected peripheral immune cells, in particular macrophages, appear to infiltrate the CNS and provoke a neuropathological response involving all cell types in the brain. Both viral and host factors, such as the viral strain and the response of the host's immune system, strongly influence the course of HIV-1 disease. Moreover, HIV-1-dependent disease processes in the periphery have a substantial effect on the pathology developing in the central nervous system (CNS), although the brain eventually harbors a distinctive viral population of its own. In the CNS, HIV-1 also initiates activation of chemokine receptors, inflammatory mediators, extracellular matrix-degrading enzymes and glutamate receptor-mediated excitotoxicity, all of which can activate numerous downstream signaling pathways and disturb neuronal and glial function. Although there have been substantial improvements in the control of viral infection in the periphery, an effective therapy for HIV-1 associated dementia (HAD) is still not in sight. This article will review recently identified injurious mechanisms potentially contributing to neuronal death in association with HIV-1 disease and discuss recent and prospective approaches for therapy and prevention of HAD.     

Diagnostic imaging of dementia in the elderly

Dementia is a frequent problem in elderly patients. More than age per se, it may influence the indication for invasive diagnostic and therapeutic procedures to treat other diseases. Here, the role of tomographic imaging methods for differential diagnosis of dementia will be reviewed briefly, with the new possibilities that became available recently. Computed tomography (CT) of the brain is used primarily to detect potentially treatable conditions, such as multiple ischemic infarcts, hematomas, hydrocephalus and brain tumors. It should be performed even at higher age if the general condition of the patient is good enough not to exclude all specific therapeutic measures. Magnetic resonance imaging (MRI) is more sensitive for ischemic white matter lesions and hippocampal atrophy and should therefore used preferentially in mildly affected patients. Functional imaging methods, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), are necessary only in clinically unclear cases to demonstrate functional impairment of association cortex.     

MRI, CT, SPECT, PET: their use in diagnosing dementia

The differential diagnosis of the dementia syndrome may pose a difficult clinical problem, since the most common dementia, Alzheimer's disease (AD), is marked by normal laboratory tests. Neuroimaging has played an important role in evaluating the demented patient, and its uses are growing. Computed tomography (CT) is useful for excluding reversible and treatable causes of dementia, such as subdural hematoma and tumor. More recently, magnetic resonance imaging (MRI) has improved our ability to diagnose vascular disease and may show the presence of cerebral infarcts and white matter disease not visible on CT. Single photon emission computed tomography (SPECT) and positron emission tomography (PET), techniques that visualize such cerebral functions as glucose metabolism and blood flow, may provide positive evidence supportive of the diagnosis of AD.     

Unraveling the mechanisms of neurotoxicity in HIV type 1-associated dementia: inhibition of neuronal synaptic transmission by macrophage secretory products

The cognitive and motor impairments of HIV-1-associated dementia (HAD) often result from neuronal damage of drop-out. In the infected human host, virus-infected immune-competent mononuclear phagocytes (MPs) (brain macrophages and microglia) are the target cells for HIV-1 and the producers of bioactive molecules that mediate neural damage. Indeed, in laboratory experiments, activated HIV-1-infected macrophages placed into human or rodent brain tissues induce neuronal apoptosis. Nonetheless, the mechanisms for neuronal dysfunction in HAD have yet to be discerned. To these ends, we studied the effects of HIV-1-infected monocyte-derived macrophage (MDM) secretions, electrophysiologically, on neuronal synaptic transmission. Bath application of HIV-1-infected MDM culture fluids onto rat hippocampal brain slices resulted in inhibition of evoked field excitatory postsynaptic potentials (EPSPs). In contrast, fluids from uninfected MDMs showed mild effects on the EPSPs. HIV-1-associated inhibition of EPSPs was enhanced by LPS activation, both for HIV-1-infected and uninfected MDMs. Importantly, paired-pulse facilitation ratio tests showed that factors secreted by HIV-1-infected MDMs acted transiently on presynaptic terminals, providing insights into the site of action and mechanism of the MDM-induced neuronal dysfunction. These results, taken together, demonstrate that factors produced as a consequence of MDM infection and activation affect neuronal synaptic transmission.     

SPECT with 99mTc-HMPAO in subjects with HIV infection: cognitive dysfunction correlates with high uptake.

We prospectively studied a cohort of 25 HIV-1 infected individuals with no clinical signs of encephalopathy with 99mTc-HMPAO-SPECT. The findings were correlated with magnetic resonance imaging (MRI), neuropsychological testing and clinical staging aiming at the early diagnosis of HIV encephalopathy by single photon emission computed tomography (SPECT). A total of 25 matched seronegative controls were subject to neuropsychological testing only. A total of 24 patients and controls were monitored for 6-46 months (mean and median 26 months). No patients developed AIDS dementia complex during the study; 3 patients developed minimal symptoms (MSK classification stage 0.5). There was a significant decline in 99mTc-HMPAO uptake over time and neuropsychological abnormalities progressed. Unexpectedly, there was a correlation of high cortical and subcortical 99mTc-HMPAO uptake and low performance in cognitive dysfunction tests, indicating a possible inflammatory reaction in the brain with increased blood flow due to HIV infection. We conclude that, in non-demented HIV-infected individuals, both the 99mTc-HMPAO uptake and functional level slowly decrease over time, but the regional cerebral blood flow decrease could be masked by a direct HIV-induced inflammatory reaction in the brain, which gives a 99mTc-HMPAO hyperfixation.     

Functional neuroimaging in acute stroke

To the present day, the first and most widespread diagnostic approach in the assessment of acute stroke remains CT scan. Its sensitivity is very high (nearly 100%) in detecting intracerebral hemorrhage in the acute period, but its capability of revealing ischemic injury in the very first hours from symptom onset is relatively poor. Since the efficacy of thrombolytic treatment in acute stroke has been suggested by the ECASS and NINDS rt-PA trials, functional neuroimaging able to distinguish potentially salvageable tissue from irreversibly injured areas has acquired primary importance. The possibility to correctly identify the tissue of the ischemic penumbra within the first hours from symptom onset is essential for correct patient selection for thrombolitic treatment. Different imaging strategies are available for the definition of perfusion deficits within the acute time window; among these are positron emission tomography (PET), single photon emission computed tomography (SPECT), Xenon CT (XeCT), dynamic CT perfusion imaging (CTP), diffusion weighted magnetic resonance imaging (DW-MRI), and perfusion weighted magnetic resonance imaging (PW-MRI). Though each technique has its advantages and limitations to present day functional MRI remains the most widespread imaging technique in the assessment of acute stroke being more accessible than both SPECT and PET, and capable of giving information on both perfusion and tissue functional status in a single imaging session. In this paper we discuss the role of functional neuroimaging in acute stroke.     

FUNCTIONAL NEUROIMAGING IN ACUTE STROKE

To the present day, the first and most widespread diagnostic approach in the assessment of acute stroke remains CT scan. Its sensitivity is very high (nearly 100%) in detecting intracerebral hemorrhage in the acute period, but its capability of revealing ischemic injury in the very first hours from symptom onset is relatively poor. Since the efficacy of thrombolytic treatment in acute stroke has been suggested by the ECASS and NINDS rt-PA trials, functional neuroimaging able to distinguish potentially salvageable tissue from irreversibly injured areas has acquired primary importance. The possibility to correctly identify the tissue of the ischemic penumbra within the first hours from symptom onset is essential for correct patient selection for thrombolitic treatment. Different imaging strategies are available for the definition of perfusion deficits within the acute time window; among these are positron emission tomography (PET), single photon emission computed tomography (SPECT), Xenon CT (XeCT), dynamic CT perfusion imaging (CTP), diffusion weighted magnetic resonance imaging (DW-MRI), and perfusion weighted magnetic resonance imaging (PW-MRI). Though each technique has its advantages and limitations to present day functional MRI remains the most widespread imaging technique in the assessment of acute stroke being more accessible than both SPECT and PET, and capable of giving information on both perfusion and tissue functional status in a single imaging session.

In this paper we discuss the role of functional neuroimaging in acute stroke.     

Imaging of Brain Function Using SPECT

Single photon emission computed tomography (SPECT) is a technique widely used in nuclear medicine for the imaging of the many organs including the skeleton and heart, as well as for whole body imaging for the detection of tumors. The use of tracers of cerebral perfusion and more recently brain neurotransmitter systems has resulted in the development of a number of applications for brain SPECT in neurology and psychiatry. Indications have been established in cases of dementia, epilepsy, neurovascular disorders, Parkinsonism, and following minor head trauma. It also has the potential to be a valuable research tool for the study of in vivo brain function. In this paper an overview will be given of the principles underlying Brain SPECT, the performance of the procedure, and its applications as a diagnostic modality and research tool.     

Molecular imaging of plaques in coronary arteries with PET and SPECT

Coronary artery disease remains a major cause of mortality. Presence of atherosclerotic plaques in the coronary artery is responsible for lu-men stenosis which is often used as an indicator for determining the severity of coronary artery disease. However, the degree of coronary lumen stenosis is not often related to compromising myocardial blood flow, as most of the cardiac events that are caused by atherosclerotic plaques are the result of vulnerable plaques which are prone to rupture. Thus, identification of vulnerable plaques in coronary arteries has become increas-ingly important to assist identify patients with high cardiovascular risks. Molecular imaging with use of positron emission tomography （PET） and single photon emission computed tomography （SPECT） has fulfilled this goal by providing functional information about plaque activity which enables accurate assessment of plaque stability. This review article provides an overview of diagnostic applications of molecular imaging tech-niques in the detection of plaques in coronary arteries with PET and SPECT. New radiopharmaceuticals used in the molecular imaging of coro-nary plaques and diagnostic applications of integrated PET/CT and PET/MRI in coronary plaques are also discussed.     

Advanced imaging in COPD: insights into pulmonary pathophysiology

Chronic obstructive pulmonary disease (COPD) involves a complex interaction of structural and functional abnormalities. The two have long been studied in isolation. However, advanced imaging techniques allow us to simultaneously assess pathological processes and their physiological consequences. This review gives a comprehensive account of the various advanced imaging modalities used to study COPD, including computed tomography (CT), magnetic resonance imaging (MRI), and the nuclear medicine techniques positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Some more recent developments in imaging technology, including micro-CT, synchrotron imaging, optical coherence tomography (OCT) and electrical impedance tomography (EIT), are also described. The authors identify the pathophysiological insights gained from these techniques, and speculate on the future role of advanced imaging in both clinical and research settings.     

Magnetic resonance imaging of the brain and spine. Is clinical efficacy established after the first decade?

STUDY OBJECTIVE: Evaluation of demonstrated clinical efficacy of magnetic resonance (MR) imaging in the central nervous system. DESIGN: Information synthesis of studies before January 1987. SETTING: Reports were classified by the level of clinical efficacy studied (technical capacity, diagnostic impacts, and therapeutic or patient outcome impacts) and were judged by the validity of their methods, especially avoidance of diagnosis review, test review, and work-up biases. MAIN RESULTS: Magnetic resonance imaging probably is superior to computed tomography for detection and characterization of posterior fossa lesions and spinal cord myelopathies, imaging in multiple sclerosis, detecting lesions in patients with refractory partial seizures, and detailed display for guiding complex therapy, as for brain tumors. In other diseases, the efficacy of MR imaging is similar to that of computed tomography (cerebrovascular, radiculopathy, and infection). Magnetic resonance imaging is less invasive than intrathecal or intravenous contrast-enhanced computed tomography and costs 20% to 300% more than computed tomography, although avoidance of hospital stays may offset some costs. Generally, the quality of MR images probably exceeds that of computed tomographic (CT) scans. However, published evidence does not show that the clinical efficacy of MR imaging is generally superior to that of existing imaging modalities such as computed tomography. Only six studies avoided major methodologic biases, and lower true-positive rates for MR imaging were reported in these studies than reported in multiply biased studies. Few studies of the potential of MR imaging for false-positive diagnosis have been done. CONCLUSIONS: Use of standards for quality of evidence leads to more conservative conclusions than those of reports describing the clinical potential of MR imaging. Some applications of MR imaging were confirmed by rigorous studies, whereas others were not well supported by reports free of methodologic biases. If the diagnostic alternative is invasive (for example, myelography and cisternography), MR imaging is preferred, but adequate diagnosis for many conditions (head trauma, simple stroke, and dementia) may not require the detail of an MR imaging study. In general, more rigorous clinical research studies are needed for new technologies such as MR imaging. Because the field of MR imaging is changing, review of its clinical efficacy will need to be revised frequently.     

Clinical applications of SPECT

The clinical use of single photon emission computed tomography (SPECT) has grown steadily over the last decade. SPECT is now an essential technique for certain studies such as cerebral blood flow imaging. Many other common nuclear medicine studies give better results when they are performed with SPECT. These include myocardial perfusion imaging with thallium-201 or the new technetium-99m perfusion agents, myocardial infarct imaging with infarct-avid agents, imaging of tumors or infections with agents such as gallium-67 or indium-111 WBC's, and certain cases of bone imaging. Still other studies such as liver/spleen imaging, most brain studies, and perhaps renal imaging may benefit from SPECT even though planar imaging gives satisfactory results. Future developments in 3D display techniques and faster computers may extend the clinical usefulness of SPECT to other areas such as pulmonary perfusion imaging and gated cardiac blood pool imaging.Abbreviations SPECT single photon emission computed tomography - WBC white blood cells - 3D three dimensional     

Central nervous system involvement in systemic lupus erythematosus patients without overt neuropsychiatric manifestations

OBJECTIVE: To verify whether features of CNS involvement can be detected in SLE patients without overt neuropsychiatric manifestations. METHODS: 114 SLE patients who had never received a diagnosis of neuropsychiatric lupus (never-NPSLE) were studied and compared to 65 SLE patients with known neuropsychiatric involvement (NPSLE). The study relied on evaluation of neurocognitive functions by means of a battery of neuropsychological tests, on psychiatric and neuropsychological assessments and on neuroimaging studies (computed tomography, magnetic resonance, single photon emission computed tomography (SPECT)). RESULTS: Clinical features, including disease duration/activity and pharmacological therapy, of never-NPSLE and NPSLE patients were similar. Short-term and long-term memory, visuo-spatial and verbal information processing were similarly compromised in never-NPSLE and in NPSLE patients; only attention was significantly more compromised in NPSLE patients. Psychiatric morbidity was higher than expected in never-NPSLE patients, although less than in the control neuropsychiatric group. Ischemic lesions, multiple small high intensity lesions and cortical atrophy, detected by CT and MR scans, as well as abnormal SPECT were also frequently detected in never-NPSLE patients. Interestingly, left parietal and occipital area hypoperfusion by SPECT was significantly more frequent in the patients with impaired visuo-spatial intelligence and short-term memory. CONCLUSIONS: Most abnormalities detected by available diagnostic tools and characteristics of neuropsychiatric SLE are also present in non-symptomatic patients. They may derive from an unexpected widespread involvement of the CNS and are not per se sufficient, in the absence of clinical manifestations, for a diagnosis of neuropsychiatric SLE.     

Comparison of coronary calcium and stress myocardial perfusion imaging in apparently healthy siblings of individuals with premature coronary artery disease

Detection of subclinical coronary atherosclerosis is possible using exercise myocardial perfusion imaging for inducible ischemia or multidetector computed tomography for coronary artery calcium (CAC), which is used to detect subclinical coronary atherosclerosis. The extent to which these screening tests converge in an asymptomatic population that is at increased risk for coronary artery disease remains unknown. We compared the concordance of findings in 260 asymptomatic middle-age siblings of hospitalized index patients <60 years of age with documented coronary artery disease. All subjects underwent maximal exercise testing with postexercise and delayed attenuation-corrected thallium single-photon emission computed tomography and multidetector computed tomography for CAC. An abnormal exercise single-photon emission computed tomographic (SPECT) result occurred in >50% of subjects with a CAC score >100, but also in 12% with no CAC, 9% with CAC scores of 1 to 10, and 20% with CAC scores of 11 to 100. In subjects with an abnormal exercise SPECT result, 59% had CAC scores < or =100. Overall, there was only a modest agreement between an abnormal exercise SPECT result and high CAC scores. In conclusion, although moderate or severe CAC is often associated with inducible ischemia, the absence of CAC or the presence of only mild CAC by no means precludes inducible myocardial ischemia. These screening tests may reflect different aspects or stages of coronary disease in an asymptomatic middle-age population.     

双嘧达莫负荷心肌201Tl和运动负荷心肌99Tcm-MIBI单光子发射计算机断层摄影在诊断心脏X综合征中的价值

目的 探讨双嘧达莫负荷心肌201T1单光子发射计算机断层摄影(SPECT)与运动负荷心肌99Tcm-甲氧基异丁基异腈(MIBI)SPECT显像在辅助诊断心脏x综合征中的价值.方法 选取临床符合心脏X综合征诊断标准患者共63例,将患者分为2组,一组行双嘧达莫负荷心肌201T1 SPECT显像,另一组行运动负荷心肌99Tcm-MIBI SPECT显像,评价两种核素心肌显像在诊断心脏X综合征中的符合率.结果 行双嘧达莫负荷心肌201T1 SPECT显像者35例,有31例出现病变部位的反向再分布,符合率为89%;行运动负荷心肌99Tcm-MIBI SPECT显像者28例,其中有24例出现负荷病变部位放射性稀疏或缺损,静息显像正常,符合率为87%.两种核素心肌灌注显像的符合率差异无统计学意义(P>0.05).结论 双嘧达莫负荷心肌201T1 SPECT显像能较直接反映心脏x综合征冠状动脉微循环病变.     

Functional significance of stenoses in coronary artery bypass grafts. Evaluation by single-photon emission computed tomography perfusion imaging, cardiovascular magnetic resonance, and angiography

OBJECTIVES: This study was designed to perform a head-to-head comparison between single-photon emission computed tomography (SPECT) and cardiovascular magnetic resonance (CMR) to evaluate hemodynamic significance of angiographic findings in bypass grafts. BACKGROUND: The hemodynamic significance of a bypass graft stenosis may not always accurately be determined from the coronary angiogram. A variety of diagnostic tests (invasive or noninvasive) can further characterize the hemodynamic consequence of a lesion. METHODS: Fifty-seven arterial and vein grafts in 25 patients were evaluated by angiography, SPECT perfusion imaging, and coronary flow velocity reserve determination by CMR. Based on angiography and SPECT, four different groups could be identified: 1) no significant stenosis (<50%), normal perfusion; 2) significant stenosis (>/=50%), abnormal perfusion; 3) significant stenosis, normal perfusion (no hemodynamic significance); and 4) no significant stenosis, abnormal perfusion (suggesting microvascular disease). RESULTS: A complete evaluation was obtained in 46 grafts. Single-photon emission computed tomography and CMR provided similar information in 37 of 46 grafts (80%), illustrating good agreement (kappa = 0.61, p < 0.001). Eight grafts perfused a territory with scar tissue. When agreement between SPECT and CMR was restricted to grafts without scar tissue, it improved to 84% (kappa = 0.68). Integration of angiography with SPECT categorized 14 lesions in group 1, 23 in group 2, 6 in group 3, and 3 in group 4. Single-photon emission computed tomography and CMR agreement per group was 86%, 78%, 100%, and 33%, respectively. CONCLUSIONS: Head-to-head comparison showed good agreement between SPECT and CMR for functional evaluation of bypass grafts. Cardiovascular magnetic resonance may offer an alternative method to SPECT for functional characterization of angiographic lesions.     

Imaging Heart Failure: Current and Future Applications

A variety of cardiac imaging tests are used to help manage patients with heart failure (HF). This article reviews current and future HF applications for the major noninvasive imaging modalities: transthoracic echocardiography (TTE), single-photon emission computed tomography (SPECT), positron emission tomography (PET), cardiovascular magnetic resonance (CMR), and computed tomography (CT). TTE is the primary imaging test used in the evaluation of patients with HF, given its widespread availability and reliability in assessing cardiac structure and function. Recent developments in myocardial strain, 3-dimensional TTE, and echo contrast appear to offer superior diagnostic and prognostic information. SPECT imaging is a common method employed to detect ischemia and viability in patients with HF; however, PET offers higher diagnostic accuracy for both. Ongoing study of sympathetic and molecular imaging techniques may enable early disease detection, better risk stratification, and ultimately targeted treatment interventions. CMR provides high-quality information on cardiac structure and function and allows the characterization of myocardial tissue. Myocardial late gadolinium enhancement allows the determination of HF etiology and may predict patient outcomes and treatment response. Cardiac CT has become a reliable means for detecting coronary artery disease, and recent advances have enabled concurrent myocardial function, perfusion, and scar analyses. Overall, available imaging methods provide reliable measures of cardiac performance in HF, and recent advances will allow detection of subclinical disease. More data are needed demonstrating the specific clinical value of imaging methods and particularly subclinical disease detection in large-scale, clinical settings.