Dynamic imaging in mild traumatic brain injury: support for the theory of medial temporal vulnerability

OBJECTIVE: To determine whether patients with mild traumatic brain injury (TBI) and persistent postconcussive symptoms have evidence of temporal lobe injury on dynamic imaging. DESIGN: Case series. SETTING: An academic medical center. PARTICIPANTS: Twenty patients with a clinical diagnosis of mild TBI and persistent postconcussive symptoms were referred for neuropsychologic evaluation and dynamic imaging. Fifteen (75%) had normal magnetic resonance imaging (MRI) and/or computed tomography (CT) scans at the time of injury. INTERVENTIONS: Neuropsychologic testing, positron-emission tomography (PET), and single-photon emission-computed tomography (SPECT). MAIN OUTCOME MEASURES: Temporal lobe findings on static imaging (MRI, CT) and dynamic imaging (PET, SPECT); neuropsychologic test findings on measures of verbal and visual memory. RESULTS: Testing documented neurobehavioral deficits in 19 patients (95%). Dynamic imaging documented abnormal findings in 18 patients (90%). Fifteen patients (75%) had temporal lobe abnormalities on PET and SPECT (primarily in medial temporal regions); abnormal findings were bilateral in 10 patients (50%) and unilateral in 5 (25%). Six patients (30%) had frontal abnormalities, and 8 (40%) had nonfrontotemporal abnormalities. Correlations between neuropsychologic testing and dynamic imaging could be established but not consistently across the whole group. CONCLUSIONS: Patients with mild TBI and persistent postconcussive symptoms have a high incidence of temporal lobe injury (presumably involving the hippocampus and related structures), which may explain the frequent finding of memory disorders in this population. The abnormal temporal lobe findings on PET and SPECT in humans may be analogous to the neuropathologic evidence of medial temporal injury provided by animal studies after mild TBI.     

The value of neuroimaging in diagnosis of epilepsy

Neuroimaging examines the relationship between abnormalities of brain function in epilepsy patients (seizures, impaired cognitive function, psychiatric co-morbidity etc.) and focal or more widespread brain pathology. Since the mid-1980s, the introduction of magnetic resonance imaging (MRI) into clinical neurology has had an impact on the diagnosis, treatment, and research of epilepsy only comparable with the advent of the electroencephalography (EEG) fifty years ago. MRI plays the important role of identifying single or multiple structural lesions responsible for the epileptic seizures. Thus, visual assessment of MRI plays an important role in the differentiation between symptomatic, cryptogenic, and idiopathic epilepsies. This diagnostic step leads to therapeutic decisions (medical treatment vs. surgery) and prognostic evaluations. If a structural lesion identified with MRI correlates with seizure-type, EEG and other clinical data, the likelihood of rendering the patient seizure free with epilepsy surgery is increased. Clinical research into epilepsy uses quantitative MRI (volumetry, T2-relaxometry, magnetic resonance spectroscopy [MRS], voxel-based morphometry) to reduce those cases initially labeled as cryptogenic. Quantitative MRI questions the belief that there is epilepsy without structural brain abnormality at all. Functional MRI (fMRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT) demonstrate changes associated with epileptic seizures and pathology, and changes associated with EEG abnormalities and their cessation. Functional neuroimaging is also used for the identification of functional brain tissue before surgery. Physiologically or pathologically active neuronal tissue is believed to be identified by glucose or oxygen consumption (PET), cerebral blood flow (PET, SPECT, perfusion MRI), and cerebral blood oxygenation (blood oxygenation level dependent [BOLD] fMRI). PET also offers the opportunity to visualize the in-vivo distribution of neuronal receptors which are implicated in the generation, the spread, and the cessation of seizures.     

Computed tomography, magnetic resonance imaging, positron emission tomography and evoked potentials at early stage of adrenoleukodystrophy

An 8 year-old-boy with adrenoleukodystrophy (ALD) was subject to an x-ray computed tomography (CT) scan, magnetic resonance imaging (MRI), positron emission tomography (PET) using 18F-fluorodeoxy glucose and evoked potential studies, about 3 months after the onset of neurologic symptoms. A CT showed decreased radiodensity over the white matter of both occipital lobes, and high density areas on the periventricular space. No contrast enhancement was observed around the low dense white matter, while occipital grey matter seemed to be almost normal. MRI demonstrated a larger and more obvious lesion of prolonged T2 relaxation time which was 170-250 msec than that detected by CT scan. The PET demonstrated wide and severe hypometabolism for glucose over the grey and the white matter of bilateral occipital lobes. The visual evoked potential (VEP) was scarcely elicitable, while the auditory brainstem response (ABR) and short latency somatosensory evoked potential (SSEP) was normal. These imaging studies suggest that extensive and profound demyelination exists in the occipital white matter. For detection of demyelinizing process, MRI may be more effective than CT in this disorder. The PET study revealed that there may have been an abnormality of the grey matter as well as the white matter in the occipital lobe. The VEP disappeared in the relatively early stage. The brainstem may not be involved at such early stage in light of normal ABR and SSEP.     

Comparison of SPECT findings and neuropsychological sequelae in carbon monoxide and organophosphate poisoning

Abnormal regional cerebral blood flow in patients with acute carbon monoxide (CO) and organophosphate (OP) poisoning was examined using (99m)Tc-hexamethylpropylene amine oxime (HMPAO) brain single photon emission computed tomography (SPECT) in fourteen patients. We evaluated the predictive significance of acute phase brain SPECT findings for long-term neuropsychological sequelae. Changes were found in the frontal, temporal, parietal lobes within the first week after both types of poisoning. The distribution of the hypoperfused cerebral areas as demonstrated by (99m)Tc-HMPAO imaging was similar in the two groups during the acute phase. Neuropsychological sequelae developed in five patients poisoned with OP and six with CO. Patients who had SPECT findings heterogeneously or in the temporal or frontal lobes displayed disorientation. Those with fronto-parietal and frontal lobe changes displayed mental confusion. Parkinsonism also was observed in patients with parieto-occipital, parietal and frontal lobe lesions. The distribution of these lesions appears to predict the long term sequelae of these poisonings, though additional studies with larger numbers of patients are needed to confirm the role of SPECT imaging in both OP and CO poisonings.     

孤独症谱系障碍相关SPECT及PET研究进展

孤独症谱系障碍（ASD）发病原因尚不明确，SPECT及PET可通过无创检测大脑血流量、葡萄糖代谢、蛋白质代谢来探究其神经生物学机制。本文对近年来ASD相关SPECT及PET研究进行综述。     

MRI检测活性心肌及其与冠状动脉造影、SPECT和PET对比研究

目的：分析MRI对冠心病患者心肌活性的诊断价值并与冠状动脉造影、SPECT和PET结果对比。方法：应用MRI对21例临床符合冠心病的患者进行检查，并将结果与冠状动脉造影、SPECT和PET检查结果对照。结果：MRI静息心肌灌注扫描检出的缺血节段比狭窄冠状动脉的供血节段少但无统计学差异（Z=-1.732，P=0．083）；比SPECT心肌灌注扫描检出的缺血节段多且有统计学差异（Z=-3．691，P=0．000）。SPECT心肌灌注扫描检出的缺血节段比狭窄冠状动脉的供血节段少且有统计学差异（Z=-3．029，P=0．002）。以正电子发射断层显像（PET）结果为标准，MR延迟扫描检测活性心肌的灵敏度为97．6％，特异度为98．4％，总符合率为98．2%，Kappa值为0．953。MR延迟扫描检出的活性心肌比PET检出的少但无统计学差异（Z=-0．209，P=0．835）。结论：MR心脏检查清晰显示心肌梗死的位置、程度和附壁血栓情况，并可对左室室壁运动进行直观显示。常规SPECT心肌灌注显像由于空间分辨率低明显低估心肌缺血范围。心肌PET显像空间分辨率低，无法显示心肌梗死的透壁程度，且不能直观显示室壁运动情况。     

Applications and software techniques for integrated cardiac multimodality imaging

Several imaging technologies are available for diagnostic cardiac imaging, such as coronary computed tomography angiography (CTA), single photon emission computed tomography (SPECT) positron emission tomography (PET) and magnetic resonance imaging (MRI). Each of these techniques offers unique advantages, but also suffers from specific limitations. Software techniques are being developed to combine cardiac images from different modalities and generate composite multimodality images, allowing better diagnosis than that possible from images analyzed separately. Hybrid scanners (SPECT/CT and PET/CT) have also been proposed for integrated cardiac imaging. Physicians are presented with integrated fused images that contain complementary information from separate scans containing physiological and anatomical information. In this review, we present the latest approaches for integration of cardiac images from multiple modalities.     

Applications and software techniques for integrated cardiac multimodality imaging

Several imaging technologies are available for diagnostic cardiac imaging, such as coronary computed tomography angiography (CTA), single photon emission computed tomography (SPECT) positron emission tomography (PET) and magnetic resonance imaging (MRI). Each of these techniques offers unique advantages, but also suffers from specific limitations. Software techniques are being developed to combine cardiac images from different modalities and generate composite multimodality images, allowing better diagnosis than that possible from images analyzed separately. Hybrid scanners (SPECT/CT and PET/CT) have also been proposed for integrated cardiac imaging. Physicians are presented with integrated fused images that contain complementary information from separate scans containing physiological and anatomical information. In this review, we present the latest approaches for integration of cardiac images from multiple modalities.     

Overview of radiopharmaceuticals for diagnosis of central nervous disorders

There are two types of imaging instruments, single-photon emission computed tomography (SPECT) and positron emission tomography (PET) that use radiopharmaceuticals for the diagnosis of brain disorders. Brain perfusion imaging agents, labeled either with 123I or 99mTc, are useful in detecting various cerebral vascular abnormalities, such as stroke and transient ischemia with SPECT. The management of other neurological disorders (i.e., in Alzheimer's, epilepsy, schizophrenia, and head trauma patients) may also be benefitted by these agents. The exact trapping mechanisms and their relationships with potential clinical applications still remain to be elucidated. Imaging studies using 18F fluorodeoxyglucose with PET is currently the most promising diagnostic tool for the evaluation of local glucose metabolism related to various disease states, such as Alzheimer's disease, brain tumor, and epilepsy. In the past few years significant progress has been made in the design and characterization of new CNS neuronal and postsynaptic receptor imaging agents for PET and SPECT. The new diagnostic agents are aimed at measurements of localization and changes of neuronal function. It is likely that these types of agents have potential for clinical application, especially in the diagnosis of psychiatric disorders that do not involve morphological changes.     

单光子发射型CT检测抑郁症患者局部脑血流的变化

背景:抑郁症患者存在着不同程度的脑血流灌注减低区,但范围不尽相同,涉及不同的大脑皮质及皮质下结构区域。目的:观察抑郁症患者局部大脑皮质血流灌注异常类型。设计:以诊断为依据的病例-对照分析。单位:上海交通大学医学院附属瑞金医院核医学科,上海交通大学医学院生物医学工程教研室,上海市普陀区精神卫生中心。对象:于1999-01/2000-12选择在普陀区精神卫生中心门诊就诊未治疗的经CCMD-2-R诊断为抑郁症12例患者为观察对象。正常对照者为与之年龄匹配的医院内工作人员19名。方法:采用SPECT检查抑郁症患者和健康人,进行双半胱乙酯脑显像,使用统计参数图对图像进行分析。首先将所有的SPECT图像转换成DICOM格式或anlysis7格式,以Talairach图谱为模版对图像进行标准化及平滑,用高斯随机理论进行统计分析与推断以评价有显著差异的区域。主要观察指标:抑郁症组与正常对照组大脑特定区域血流灌注的区别和平均局部脑血流图像的变化。结果:抑郁症者12例和正常健康人19名均完成检测,进入结果分析。统计参数图分析显示抑郁症患者的双侧额叶、左侧颞上回、左侧边缘叶钩回(Brodmannarea20)、左侧丘脑乳头体、右侧扣带回、右侧壳核血流灌注下降。抑郁症患者的右侧中间额回,右侧上颞回,右侧枕叶,左侧中间额回血流灌注升高。结论:抑郁症患者额叶、颞叶及边缘系统局部脑血流发生了明显的变化。     

Atypical lexicosemantic function of extrastriate cortex in autism spectrum disorder: evidence from functional and effective connectivity

Previous studies have suggested atypically enhanced activity of visual cortex during language processing in autism spectrum disorder (ASD). However, it remains unclear whether visual cortical participation reflects isolated processing within posterior regions or functional cooperation with distal brain regions, such as left inferior frontal gyrus (LIFG). We addressed this question using functional connectivity MRI (fcMRI) and structural equation modeling in 14 adolescents and adults with ASD and 14 matched typically developing (TD) participants. Data were analyzed to isolate low-frequency intrinsic fluctuations, by regressing out effects of a semantic decision task. For a right extrastriate seed derived from the strongest cluster of atypical activation in the ASD group, widespread effects of increased connectivity in prefrontal and medial frontal lobes bilaterally were observed for the ASD group, compared to the TD group. A second analysis for a seed in LIFG, derived from pooled activation effects in both groups, also yielded widespread effects of overconnectivity in the ASD group, especially in temporal lobes. Structural equation modeling showed that whereas right extrastriate cortex did not impact function of language regions (left and right IFG, left middle temporal gyrus) in the TD model, it was an integral part of a language circuit in the ASD group. These results suggest that atypical extrastriate activation during language processing in ASD reflects integrative (not isolated) processing. Furthermore, our findings are inconsistent with previous reports of functional underconnectivity in ASD, probably related to removal of task effects required to isolate intrinsic low-frequency fluctuations.     

Non-invasive Imaging in Gene Therapy.

Several methods are available for non-invasive imaging of gene delivery and transgene expression, including magnetic resonance imaging (MRI), single photon emission tomography (SPECT)/positron emission tomography (PET), and fluorescence and bioluminescence imaging. However, these imaging modalities differ greatly in terms of their sensitivity, cost, and ability to measure the signal. Whereas MRI can produce a resolution of approximately 50 mum, optical imaging achieves only 3-5 mm but outperforms MRI in terms of the cost of the imaging device. Similarly, SPECT and PET give a resolution of only 1-2 mm but provide for relatively easy quantitation of the signal and need only nanograms of probe, compared with the microgram or milligram levels required for MRI and optical imaging. To develop safer and more efficient gene delivery vectors, it is essential to perform rigorous in vivo experiments, to image particle biodistribution and transduction patterns, and to quantify the transgene expression profile. Differences between modalities have a significant effect on the resultant imaging resolution for gene therapy. This review describes the methodologies in use and highlights recent key approaches using the latest imaging modalities in gene therapy. Future trends in gene therapy imaging are also discussed.     

Single-photon emission computed tomography for cerebral blood flow in school phobia

To investigate the correlation between abnormalities of regional cerebral blood flow and psychosomatic symptoms in school phobia, we examined cerebral blood flow in 55 patients with school phobia using single-photon emission computed tomography (SPECT) with 111 MBq ¹²³I-iodoamphetamine. The relationship between neuropsychological examination scores and SPECT findings was also examined. None of our patients exhibited evidence of focal structural abnormalities on magnetic resonance imaging. Blood flow, expressed as the corticocerebellar ratio (CCR) in the frontal, temporal, and occipital lobes, was markedly lower in patients with general fatigue, headache, and memory disturbance than in healthy adult subjets studied by another investigator and used as reference values in this study. However, parietal CCRs were higher in children with school phobia than in adult volunteers. These findings suggest that in patients with school phobia, the clinical psychosomatic symptoms may be closely related to decrease cerebral blood flow, especially in the frontal lobe. The relationship between symptoms of depression in our patients, measured using the self-rating depression scale score, and CCR was not significant.     

Estrogen- and tamoxifen-associated effects on brain structure and function

We evaluated the effects of estrogen and tamoxifen, a selective estrogen receptor modulator, on positron emission tomography (PET) measures of brain glucose metabolism and magnetic resonance imaging (MRI) measures of hippocampal atrophy. Three groups of postmenopausal women were studied, women taking estrogen (ERT+), women with breast cancer taking tamoxifen (TAM), and women not taking estrogen or tamoxifen (ERT-). All subjects received a PET scan, an MRI scan, and cognitive testing. The TAM group showed widespread areas of hypometabolism in the inferior and dorsal lateral frontal lobes relative to the other two groups. The ERT- group showed lower metabolism in the inferior frontal cortex and temporal cortex with respect to the ERT+ group. The TAM group also showed significantly lower semantic memory scores than the other two groups. Finally, the TAM group had smaller right hippocampal volumes than the ERT+ group, an effect that was of borderline significance. Both right and left hippocampal volumes were significantly smaller than the ERT+ group when a single outlier was removed. The ERT- group had hippocampal volumes that were intermediate to the other two groups. These findings provide physiological and anatomical evidence for neuroprotective effects of estrogen.     

Brain imaging in depression

Structural brain imaging studies in major depression have revealed decreased hippocampal volume, decreased frontal lobe volume, decreased basal ganglia volume and increased subcortical hyperintensity lesions(SCH). Decreased hippocampal volume is thought to be related to hypercortisolemia. SCH is related to poor treatment response and clinical symptoms, thus has some value in clinical decision making. Functional brain imaging studies suggested decreased blood flow and metabolism in the frontal lobes and basal ganglia by positron emission tomography and single photon emission tomography, decreased adenosine triphosphate measured by 31P-magnetic resonance spectroscopy(MRS) in the frontal lobes and basal ganglia, and increased choline containing compounds observed by proton MRS.     

Coregistration of Magnetic Resonance and Single Photon Emission Computed Tomography Images for Noninvasive Localization of Stem Cells Grafted in the Infarcted Rat Myocardium

This paper demonstrates the application of mutual information based coregistration of radionuclide and magnetic resonance imaging (MRI) in an effort to use multimodality imaging for noninvasive localization of stem cells grafted in the infarcted myocardium in rats. Radionuclide imaging such as single photon emission computed tomography (SPECT) or positron emission tomography (PET) inherently has high sensitivity and is suitable for tracking of labeled stem cells, while high-resolution MRI is able to provide detailed anatomical and functional information of myocardium. Thus, coregistration of PET or SPECT images with MRI will map the location and distribution of stem cells on detailed myocardium structures. To validate this coregistration method, SPECT data were simulated by using a Monte Carlo-based projector that modeled the pinhole-imaging physics assuming nonzero diameter and photon penetration at the edge. Translational and rotational errors of the coregistration were examined with respect to various SPECT activities, and they are on average about 0.50 mm and 0.82°, respectively. Only the rotational error is dependent on activity of SPECT data. Stem cells were labeled with ¹¹¹Indium oxyquinoline and grafted in the ischemic myocardium of a rat model. Dual-tracer small-animal SPECT images were acquired, which allowed simultaneous detection of ¹¹¹In-labeled stem cells and of [^99mTc]sestamibi to assess myocardial perfusion deficit. The same animals were subjected to cardiac MRI. A mutual-information-based coregistration method was then applied to the SPECT and MRIs. By coregistration, the ¹¹¹In signal from labeled cells was mapped into the akinetic region identified on cine MRIs; the regional perfusion deficit on the SPECT images also coincided with the akinetic region on the MR image.     

I-124-PET/US Fusion Imaging in Comparison to Conventional Diagnostics and Tc-99m Pertechnetate SPECT/US Fusion Imaging for the Function Assessment of Thyroid Nodules

The purpose of this study is to investigate I-124 positron emission tomography (PET)/ultrasound (US) fusion imaging for function assessment of thyroid nodules. In 70 patients, 201 lesions were examined with conventional diagnostics (CD) (thyroid US, laboratory findings and Tc-99m pertechnetate scintigraphy), Tc-99m pertechnetate single photon emission computed tomography (SPECT) and I-124 PET/computed tomography (CT). Subsequently, US fusion imaging (SPECT/US and PET/US) was performed by three experienced investigators. Patients referred for thyroid diagnostics in a clinical routine setting were included in this study if CD produced equivocal results. PET/US was superior to CD and SPECT/US in 96% and 86%, respectively, and ambiguous findings in CD were clarified by PET/US in 96% of the 70 patients. Regarding nodule-based function assessment, 10% (66%), 39% (14%) and 71% (4%) of the 201 lesions were rated with absolute certainty (equivocal or uncertain) using CD, SPECT/US and PET/US, respectively (p < 0.001). PET/US has the potential to improve the function assessment of thyroid nodules in comparison to CD.     

Extraction of epileptogenic foci from PET and SPECT images by fuzzy modeling and data fusion

During the presurgical evaluation of medically intractable epilepsy, isotopic functional imagery provides an increasing amount of data concerning the potential location of the focus. The aim of this study is to facilitate the surgical decision by presenting an image fusion method able to extract epileptogenic foci from periictal single photon emission computed tomography (SPECT), interictal SPECT, fluoro-desoxy-glucose (FDG) position emission tomography (PET), and flumazenil PET. After spatial coregistration, the images are converted into fuzzy maps whose membership functions indicate the pathological degree of each voxel, according to each modality. These maps are then fused together thanks to a combination operator managing uncertainty (due to the sensitivity) and imprecision (due to poor resolution and partial volume effect) of the images. In the framework of possibilistic theory, this operator mimics the way the physicians evaluate and compare the various exams. The technique was successfully tested on simulated images with well-defined abnormalities, in terms of size and intensity. A preliminary clinical study was also performed and gave results in accordance with the "gold standard" investigation (deep electrodes or postsurgical outcome) in 11 patients out of 12.     

Tumor Hypoxia Imaging

There is a need to measure tumor hypoxia in assessing the aggressiveness of tumor and predicting the outcome of therapy. A number of invasive and noninvasive techniques have been exploited to measure tumor hypoxia, including polarographic needle electrodes, immunohistochemical staining, radionuclide imaging (positron emission tomography [PET] and single-photon emission computed tomography [SPECT]), magnetic resonance imaging (MRI), optical imaging (bioluminescence and fluorescence), and so on. This review article summarizes and discusses the pros and cons of each currently available method for measuring tissue oxygenation. Special emphasis was placed on noninvasive imaging hypoxia with emerging new agents and new imaging technologies to detect the molecular events that are relevant to tumor hypoxia.     

Metastasis of breast cancer to liver through direct lymphatic drainage: a case report

Breast cancer liver metastasis (BCLM) is considered to occur by hematogenous spread of primary breast cancer cells. We herein present a case of lymphatic BCLM that was confirmed by preoperative imaging for sentinel lymph node biopsy (SLNB). A woman in her early 70s was diagnosed with clinical stage T2N0M0 invasive lobular cancer of the left breast. She underwent mastectomy with SLNB. Preoperative lymphoscintigraphy showed intense accumulation of isotope in the upper abdomen, corresponding to segment IV of the liver on single-photon emission computed tomography/computed tomography (SPECT/CT). However, no abnormalities were detected on magnetic resonance imaging. At 2.5 years postoperatively, the patient’s serum CA15-3 concentration was elevated, and positron emission tomography/computed tomography (PET/CT) showed a solitary liver metastasis. The PET/CT findings were similar to the SPECT/CT findings obtained 2.5 years earlier, indicating that the BCLM had developed lymphatically. To the best of our knowledge, this is the first case report of lymphatic BCLM proven by imaging examination.