Mimics of brain tumor on neuroimaging: part II

Brain tumor is a distinct pathological entity that differs from other diseases, including cerebrovascular, demyelinating, inflammatory, infectious, and various miscellaneous diseases. Insidious onset and gradual progression of signs and symptoms are common in patients with brain tumors, whereas the onset of cerebrovascular diseases is usually acute or sudden. Patients with demyelinating, inflammatory, or infectious diseases show subacute onset. Differentiation of brain tumors from other disorders is usually possible from the clinically and radiologically characteristic features. However, in some diseases other than brain tumors, an atypical clinical course and/or radiological findings may suggest or simulate those of brain tumors. The diagnosis of brain tumor is confirmed histopathologically, and appropriate therapies are given to the patient based on the histopathological type and grade of the tumor. In order to obtain a specimen for histopathological examination, surgical intervention is required. Other diseases are usually diagnosed clinically and radiologically. Invasive procedures should be avoided in making a diagnosis. Therefore, differentiation of brain tumors from other diseases is a critical issue for neuroimaging. Detailed inspection of images is necessary, and characteristic findings, and additional imaging methods, such as diffusion-weighted imaging, are often helpful for the differential diagnosis. We assess the imaging findings of diseases simulating brain tumors and review the literature.     

Noninvasive molecular neuroimaging using reporter genes: part I, principles revisited

SUMMARY: In this first article, we review the basic principles of using reporter genes for molecular imaging of the brain in living subjects. This approach is emerging as a valuable tool for monitoring gene expression in diverse applications in laboratory animals, including the study of gene-targeted and trafficking cells, gene therapies, transgenic animals, and more complex molecular interactions within the central nervous system. Further development of more sensitive and selective reporters, combined with improvements in detection technology, will consolidate the position of in vivo reporter gene imaging as a versatile method for greater understanding of intracellular biologic processes and underlying molecular neuropathology and will potentially establish a future role in the clinical management of patients with neurologic diseases.     

The Neuroimaging Center of the Pediatric Brain Tumor Consortium-collaborative neuroimaging in pediatric brain tumor research: a work in progress

As an essential part of the National Cancer Institute (NCI)-funded Pediatric Brain Tumor Consortium (PBTC), the Neuroimaging Center (NIC) is dedicated to infusing the study of pediatric brain tumors with imaging "best practice" by producing a correlative research plan that 1) resonates with novel therapeutic interventions being developed by the wider PBTC, 2) ensures that every PBTC protocol incorporates an imaging "end point" among its objectives, 3) promotes the widespread implementation of standardized technical protocols for neuroimaging, and 4) facilitates a quality assurance program that complies with the highest standards for image data transfer, diagnostic image quality, and data integrity. To accomplish these specific objectives, the NIC works with the various PBTC sites (10 in all, plus NCI/ National Institute of Neurological Diseases and Stroke representation) to ensure that the overarching mission of the consortium--to better understand tumor biology and develop new therapies for central nervous system tumors in children--is furthered by creating a uniform body of imaging techniques, technical protocols, and standards. Since the inception of the NIC in 2003, this broader mandate has been largely accomplished through a series of site visits and meetings aimed at assessing prevailing neuroimaging practices against NIC-recommended protocols, techniques, and strategies for achieving superior image quality and executing the secure transfer of data to the central PBTC. These ongoing evaluations periodically examine investigations into targeted drug therapies. In the future, the NIC will concentrate its efforts on improving image analysis for MR imaging and positron-emission tomography (PET) and on developing new ligands for PET; imaging markers for radiation therapy; and novel systemic, intrathecal, and intralesional therapeutic interventions.     

Targeted alpha therapy: part I

The possibility of pinpointing biological targets, and thereby potentially targeting and eradicating small tumors or even single cancer cells, is a tantalizing concept that has been discussed since the magic-bullet concept was first presented by Paul Erlich in the beginning of the 20th century in connection with his work on tissue staining for histological examinations and the work by Kohler and Milstein on antibody production published in 1975. This concept now seems feasible through the use of highly specific targeting constructs, chemical labeling of radioactive substances to these targeting constructs that results in high specific activities, radioimmunocomplexes with good stability even after injection, and the use of radionuclides emitting alpha( α)-particles having exceedingly high ionizing density and, therefore, a high probability of killing cells along its track in tissue. The short range of the emitted α-particles makes them even more interesting by minimizing unwanted irradiation of normal tissue surrounding the targeted cancer cells of interest, assuming high specificity of the targeting construct and good stability of the chemical bonds between the targeting construct and the α-particle emitter. Targeted Alpha Therapy (TAT), in which an α-particle emitting radionuclide is specifically directed to the biological target, is gaining more attention as new targets, targeting constructs, chemical labeling techniques, and α-particle emitters are, respectively, identified, constructed, developed, and made available. Results and improvements are now being published at an increasing rate and the number of conceivable applications is expanding, especially in the field of cancer treatment. Therefore, it is of utmost importance to provide an overview of the overall progress in the research field of TAT on a regular basis. However, problems such as limited or delayed diffusion of the α-radioimmunocomplex and inhomogeneous activity distributions in the targeted tumors, resulting in inhomogeneous absorbed dose distributions, are challenges that need to be addressed. These challenges need to be overcome before TAT becomes a standard treatment for diseases such as micrometastatic cancer. Hopefully, when enough funding will be provided and, hence, more treatment strategies of TAT will reach the clinical level the importance to conduct controlled, randomized trials with sufficient patient numbers, enabling statistical significance to occur must be emphasized in order to be able to properly compare and evaluate different approaches. In this issue, of the two hot-topic issues for targeted alpha therapy, articles discuss the recent developments in radionuclide availability, biomolecular targeting, labeling chemistry, and dosimetry for the most promising α-particle emitters. In the first article, Zalutsky et al. discuss the possibilities and limitations of using the promising α-particle emitter, 211At, and emphasize the need for funding new cyclotrons and prioritizing beam-times of already existing cyclotrons to improve the availability of 211At. Haddad et al. describe the status of the ARRONAX project through which a number of important nuclear medicine radionuclides will be produced, including some of those suitable for TAT. Relevant targeting constructs and their associated antigens used today and candidates for use in the future are discussed by Olafsen et al. in the third article. The next article, by Scott Wilbur, discusses chemical and radiochemical issues of radiolabeling using α-particle emitting radionuclides, e.g. factors that are important in selecting chelation or bonding reagents during the development of α-particle emitting radiopharmaceuticals. Lindegren at al. continue the discussion of chemical considerations in the following article, but focuses on pre-targeting techniques, which will hopefully enhance both the activity distribution in the targeted tumor and the tumor-to-normal tissue absorbed dose ratio. The two final articles discuss different aspects of the dosimetry related to α-particles. The article by Sgouros et al. discusses how knowledge of the microscopic distribution of α-particle emitters is necessary to perform correct dosimetry, as well as the importance of the translation of activity distributions obtained in pre-clinical studies to the human situation, which requires micro-scale models of the source-target geometry at human dimensions according to the authors. Chouin et al. focus in the following article on the microdosimetry of α-particles. The authors present basic concepts and some applications of the microdosimetry for TAT, and conclude microdosimetry should only be considered when alternative approaches fail to provide an account of a given biological endpoint. The intention of this particular hot-topic issue is to present an up-to-date overview of key areas in the research field of TAT, i.e. radionuclides available, targeting constructs, labeling chemistry, and dosimetry. This issue will hopefully be followed by similar ones jointly produced by contributions from the research community active in the field, of which most researchers are participating in these two particular issues, i.e. Targeted Alpha Therapy - Part I and II.     

Nontraumatic spine disorders: part I

This article discusses several critical nontraumatic emergencies that involve the spine. Metastatic disease, infection of the disc and epidural space, acute disc herniation, epidural hematoma, and epidural lipomatosis may all present with symptoms ranging from localized pain to more severe neurologic sequelae. Several of these entities may progress to irreversible myelopathy or death if the diagnosis is not made in a timely manner. Appropriate radiologic evaluation and accurate interpretation are required to guide necessary treatment for these entities. Clinical presentation, etiology, radiologic findings, and pitfalls of interpretation of these conditions and related entities will be presented.     

肝移植术后认知与脑改变的多模态神经成像

肝性脑病是终末期肝硬化的重要并发症,导致病人出现一系列神经及认知功能改变。肝移植术后病人在肝功能恢复的同时其认知功能也可明显改善。MRI可以从脑代谢、结构及功能方面更进一步揭示肝硬化病人移植术后认知及脑改变情况。综述肝移植术后认知改变的研究现状以及最新的多模态MRI技术在术后脑改变中的应用,及其在揭示术后认知恢复及残存损害的神经机制中的价值。     

Clinical use of intensity-modulated radiotherapy: part I

Intensity-modulated radiotherapy (IMRT) is a novel conformal radiotherapy technique which is gaining increasing clinical use worldwide. This article aims to summarize the published data pertaining to clinical indications of this therapy for head and neck, central nervous system, and lung tumours. The main indications in head and neck cancer are parotid gland sparing and dose escalation to tumours close to organs at risk. For central nervous system tumours, IMRT has been used to reduce normal tissue radiation by more conformal dose distributions. To date, the majority of reports concern patients treated in the context of clinical trials, and for most tumour types longer term follow up of treated patients will be required to confirm the clinical benefits of IMRT.     

Noncardiac findings on cardiac CT part I: Pros and cons

Cardiac computed tomography (CT) has evolved into an effective imaging technique for the evaluation of coronary artery disease in selected patients. Two distinct advantages over other noninvasive imaging modalities include its ability to evaluate directly the coronary arteries and to provide an opportunity to evaluate extracardiac structures, such as the lungs and mediastinum. Some centers reconstruct a small field of view (FOV) cropped around the heart, but a full FOV (from skin to skin in the irradiated area) is obtainable in the raw data of every scan so that clinically relevant noncardiac findings are identifiable. Debate in the scientific community has centered on the necessity for this large FOV evaluation. A review of noncardiac structures provides the opportunity to make alternative diagnoses that may account for the patient's presentation or to detect important but clinically silent problems such as lung cancer. Critics argue that the yield of biopsy-proven cancers is low and that the follow-up of incidental noncardiac findings is expensive, resulting in increased radiation exposure and possibly unnecessary further testing. In this two-part review we outline the issues surrounding the concept of the noncardiac read looking for noncardiac findings on cardiac CT. Part I focuses on the pros and cons of the practice of identifying noncardiac findings on cardiac CT.     

FDG-PET on irradiated brain tumor: ten years' summary

Purpose: To evaluate FDG-PET in post-radiotherapy differentiation of tumor recurrence/malignant degeneration and radiation reaction, and to assess the role of PET in terms of survival.

Material and Methods: 117 consecutive patients with a total of 156 FDG-PET examinations with positive but non-diagnostic MRI and/or CT were included. Final diagnosis was based on histopathology or correlated with radiologic and clinical follow-up. Brain metastases from lung carcinomas were further studied separately. Survival time was analysed using the Kaplan-Meier method.

Results: There were 61 true-positive, 2 false-positive, 15 false-negative, and 51 true-negative PET examinations; 5 positive and 22 negative PET examinations were indeterminate. The positive predictive value of a PET examination was 96% in all and 100% in brain metastases from lung carcinoma. The negative predictive value based on the histopathologic results was 55.6%. Survival time was significantly longer in patients with negative PET.

Conclusion: FDG-PET is a valuable tool in the detection of tumor recurrence, especially lung carcinoma metastasis. FDG uptake is a prognostic marker.     

Noninvasive molecular neuroimaging using reporter genes: part II, experimental, current, and future applications

SUMMARY: In this second article, we review the various strategies and applications that make use of reporter genes for molecular imaging of the brain in living subjects. These approaches are emerging as valuable tools for monitoring gene expression in diverse applications in laboratory animals, including the study of gene-targeted and trafficking cells, gene therapies, transgenic animals, and more complex molecular interactions within the central nervous system. Further development of more sensitive and selective reporters, combined with improvements in detection technology, will consolidate the position of in vivo reporter gene imaging as a versatile technique for greater understanding of intracellular biologic processes and underlying molecular neuropathology and will potentially establish a future role in the clinical management of patients with neurologic diseases.     

The neuroimaging evidence for chronic brain damage due to boxing

A number of imaging techniques have been used to investigate changes produced in the brain by boxing. Most morphological studies have failed to show significant correlations between putative abnormalities on imaging and clinical evidence of brain damage. Fenestration of the septum pellucidum, with formation of a cavum, one of the most frequent observations, does not appear to correlate with neurological or physiological evidence of brain damage. Serial studies on large groups may be more informative. Magnetic resonance spectroscopy and cerebral blood flow studies have been reported in only small numbers of boxers; serial studies are not available to date. Received: 5 August 1991/Accepted: 5 August 1999     

Role of neuroimaging in Alzheimer's disease, with emphasis on brain perfusion SPECT.

Structural MRI and functional imaging by SPECT as well as 18F-FDG PET are widely used in the diagnosis of Alzheimer's disease (AD). Metabolic and perfusion reductions in the parietotemporal association cortex are recognized as a diagnostic pattern for AD. Outstanding progress in the diagnostic accuracy of these modalities has been achieved with statistical analysis on a voxel-by-voxel basis after anatomic standardization of individual scans to a standardized brain volume template instead of visual inspection or a volume-of-interest technique. In a very early stage of AD, this statistical approach revealed losses of gray matter in the entorhinal and hippocampal areas and hypometabolism or hypoperfusion in the posterior cingulate cortex and precuneus. This statistical approach also offers a prediction of the conversion from mild cognitive impairment (MCI) to AD. The presence of hypometabolism or hypoperfusion in parietal association areas and entorhinal atrophy at the MCI stage have been reported to predict a rapid conversion to AD. A recent advance in voxel-based statistical analysis has markedly enhanced the value of brain perfusion SPECT in diagnosing early AD at the stage of MCI.     

基于神经影像的复杂脑网络技术用于阿尔兹海默症的研究进展

近年来,人工智能技术被广泛地应用于阿尔兹海默症（AD）的计算机辅助诊断和疾病机理研究,基于图论的复杂网络分析技术是其中一种常见的数据挖掘方法,通过结构磁共振、功能磁共振和PET等神经成像手段获取多模态脑影像信息,结合复杂网络分析方法发现,AD患者大脑结构/功能网络存在拓扑异常改变。这一发现为AD的早期诊断和机理研究提供了新思路。笔者综述了复杂网络分析技术在AD脑结构和功能影像中的临床应用现状,并对其发展趋势进行了展望。     

Postmortem chemistry update part I

Postmortem chemistry is becoming increasingly essential in the forensic pathology routine and considerable progress has been made over the past years. Biochemical analyses of vitreous humor, cerebrospinal fluid, blood and urine may provide significant information in determining the cause of death or in elucidating forensic cases. Postmortem chemistry may essentially contribute in the determination of the cause of death when the pathophysiological changes involved in the death process cannot be detected by morphological methods (e.g. diabetes mellitus, alcoholic ketoacidosis and electrolytic disorders). It can also provide significant information and useful support in other forensic situations, including anaphylaxis, hypothermia, sepsis and hormonal disturbances. In this article, we present a review of the literature that covers this vast topic and we report the results of our observations. We have focused our attention on glucose metabolism, renal function and electrolytic disorders.     

MRI of hypertrophic cardiomyopathy: part I, MRI appearances

OBJECTIVE: We present a two-part review about the use of MRI in patients with hypertrophic cardiomyopathy (HCM). This article, Part 1, focuses on the MRI appearances of HCM. CONCLUSION: MRI has proven to be an important tool for the evaluation of patients suspected of having HCM because it can readily diagnose those with phenotypic expression of the disorder and can potentially identify the subset of patients at risk of sudden cardiac death.     

创伤后应激障碍脑功能神经影像学研究和进展

创伤后应激障碍是个体经历严重的创伤性事件(如战争、受虐)后产生的严重的精神障碍。近年来,脑神经影像研究尤其是功能神经影像学研究在创伤后应激障碍中的应用日益增多,功能神经影像技术有利于观察创伤后应激障碍功能脑区以及神经环路的异常。本文综述功能神经影像技术(功能磁共振成像,正电子发射断层扫描,和单光子发射计算机体层扫描)在创伤后应激障碍研究中的重要发现,并提出今后可能的研究方向。