Susceptibility-Weighted MR Imaging Hypointense Rim in Progressive Multifocal Leukoencephalopathy: The End Point of Neuroinflammation and a Potential Outcome Predictor.

BACKGROUND AND PURPOSE: Progressive multifocal leukoencephalopathy (PML) represents a life-threatening demyelinating disorder of the brain caused by reactivation of a rare opportunistic infection with JC Polyomavirus. The aims of this study were to describe the incidence of a susceptibility-weighted imaging hypointense rim in patients with multifocal leukoencephalopathy and to explore the histologic correlates and prognostic value of the rim with regard to the clinical outcome. MATERIALS AND METHODS: This retrospective study included 18 patients with a definite diagnosis of progressive multifocal leukoencephalopathy. Ten patients were HIV-positive, 3 patients had natalizumab-associated progressive multifocal leukoencephalopathy, 1 patient had multiple myeloma, 3 patients had a history of lymphoma, and 1 was diagnosed with acute myeloid leukemia. Patients were divided into short- (up to 12 months) and long-term (>12 months) survivors. A total of 93 initial and follow-up MR imaging examinations were reviewed. On SWI, the presence and development of a hypointense rim at the periphery of the progressive multifocal leukoencephalopathy lesions were noted. A postmortem histologic examination was performed in 2 patients: A rim formed in one, and in one, there was no rim. RESULTS: A total of 73 progressive multifocal leukoencephalopathy lesions were observed. In 13 (72.2%) patients, a well-defined thin, linear, hypointense rim at the periphery of the lesion toward the cortical side was present, while in 5 (27.8%) patients, it was completely absent. All 11 long-term survivors and 2 short-term survivors presented with a prominent SWI-hypointense rim, while 5/7 short-term survivors did not have this rim. CONCLUSIONS: The thin, uniformly linear, gyriform SWI-hypointense rim in the paralesional U-fibers in patients with definite progressive multifocal leukoencephalopathy might represent an end-point stage of the neuroinflammatory process in long-term survivors.

[Physico-chemical and toxicological profile of gadolinium chelates as contrast agents for magnetic resonance imaging]. / Physico-chimie et profil toxicologique d'agents de contraste pour l'imagerie par résonance magnétique, les chélates de gadolinium.

Gadolinium chelates (GC) are contrast agents widely used to facilitate or to enable diagnosis using magnetic resonance imaging (MRI). From a regulatory viewpoint, GC are drugs. GC have largely contributed to the success of MRI, which has become a major component of clinician's diagnostic armamentarium. GC are not metabolised and are excreted by the kidneys. They distribute into the extracellular compartment. Because of its high intrinsic toxicity, gadolinium must be administered as a chelate. GC can be classified according to two key molecular features: (a) nature of the chelating moiety: either macrocyclic molecules in which gadolinium is caged in the pre-organized cavity of the ligand, or linear, open-chain molecules, (b) ionicity: Gd chelates can be ionic (meglumine or sodium salts) or non-ionic. The thermodynamic and kinetic stabilities of the various GCs differ according to these structural characteristics. The kinetic stability of macrocyclic GCs is much higher than that of linear GCs and the thermodynamic stability of ionic GCs is generally higher than that of non-ionic GC, thus leading to a lower risk of gadolinium dissociation. This class of drugs has enjoyed an excellent reputation in terms of safety for a long time, until a causal link with a recently-described serious disease, nephrogenic systemic fibrosis (NSF), was evidenced. It is acknowledged that the vast majority of NSF cases are related to the administration of some linear CG in renally-impaired patients. Health authorities, worldwide, released recommendations which drastically reduced the occurrence of new cases.

How to image patients with spine pain.

Different radiological methods play an important role in the work-up of patients complaining of spine pain. Depending on the symptoms and the suspected underlying etiology different methods are selected. In the following presentation we briefly present the different radiological and magnetic resonance tomography methods that are at hand, give some guidance in which method to use, and present the typical imaging findings in some of the most common conditions that presents with spine pain.

CNS-immune reconstitution inflammatory syndrome in the setting of HIV infection, part 1: overview and discussion of progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome and cryptococcal-immune reconstitution inflammatory syndrome.

SUMMARY: While uncommon, CNS-IRIS developing after the initiation of HAART in the setting of HIV-related severe immunosuppression is characterized by an intense inflammatory reaction to dead or latent organisms or to self-antigens due to a heightened but dysregulated immune response. While this reaction can range from mild to fulminating, encompassing a very wide clinical spectrum, it is important to recognize because changes in medical management may be necessary to prevent neurologic decline and even death. Once contained, however, this inflammatory response can be associated with improved patient outcome as immune function is restored. Among the infectious organisms that are most commonly associated with CNS-IRIS are the JC virus and Cryptococcus organisms, which will be the subject of this review. CD8 cell infiltration in the leptomeninges, perivascular spaces, blood vessels, and even parenchyma seems to be the pathologic hallmark of CNS-IRIS. While recognition of CNS-IRIS may be difficult, the onset of new or progressive clinical symptoms, despite medical therapy and despite improved laboratory data, and the appearance on neuroimaging studies of contrast enhancement, interstitial edema, mass effect, and restricted diffusion in infections not typically characterized by these findings in the untreated HIV-infected patient should raise the strong suspicion for CNS-IRIS. While CNS-IRIS is a diagnosis of exclusion, the neuroradiologist can play a critical role in alerting the clinician to the possibility of this syndrome.

CNS-immune reconstitution inflammatory syndrome in the setting of HIV infection, part 2: discussion of neuro-immune reconstitution inflammatory syndrome with and without other pathogens.

SUMMARY: While the previous review of CNS-IRIS in the HIV-infected patient on highly active antiretroviral therapy (Part 1) dealt with an overview of the biology, pathology, and neurologic presentation of this condition and a discussion of the atypical imaging findings in PML-IRIS and cryptococcal meningitis-IRIS due to the robust inflammatory response, the current review (Part 2) discusses the imaging findings in other commonly encountered organisms seen in association with CNS-IRIS, namely, VZV, CMV, HIV, Candida organisms, Mycobacterium tuberculosis, and Toxoplasma gondii. Also described is the imaging appearance of CNS-IRIS when not associated with a particular organism. Recognition of these imaging findings will give credence to the diagnosis of CNS-IRIS and will allow the clinician to institute changes in medical management, if necessary, so that immune reconstitution and improved patient outcome can occur with time.

Parallel imaging of the cervical spine at 3T: optimized trade-off between speed and image quality.

BACKGROUND AND PURPOSE: Patients with cervical spine syndrome often experience pain during the MR examination. Our aim was to compare the quality of cervical spine MR images obtained by parallel imaging with those of nonaccelerated images, with the goal of shortening the examination time while preserving adequate image quality. MATERIALS AND METHODS: A phantom study and examinations of 10 volunteers and 26 patients were conducted on a clinical 3T scanner. Acquisitions included axial T2WI, sagittal T2WI, T1WI, and T2TIRM sequences. Nonaccelerated sequences and accelerated sequences with different numbers of averages and different accelerations, with a scanning time reduction of 67%, were performed. For quantitative analysis, the SNR was obtained from the phantom measurements, and the NU was calculated from the volunteer measurements. For qualitative analysis, 3 independent readers assessed the delineation of anatomic structures in volunteers and the visibility of degenerative disease in patients. RESULTS: In the phantom study, as expected, the SNR of the nonaccelerated images was higher than the SNR of the same sequence with parallel imaging. In vivo, the NU was higher when applying fewer averages or parallel imaging, compared with the nonaccelerated images. The analysis of the subjective parameters in the volunteers and patients showed that a scanning time of 48% of the original protocol could be obtained by combining the following sequences: sagittal T1WI with 1 average; sagittal T2WI with acceleration factor 3; sagittal T2TIRM with acceleration factor 2; and axial T2* GRE with acceleration factor 2. CONCLUSIONS: Parallel imaging of the cervical spine at 3T allows shortening of the examination time by 52%, preserving adequate image quality.

Diffusion-weighted MR imaging within 24 h post-injury after traumatic spinal cord injury: a qualitative meta-analysis between T2-weighted imaging and diffusion-weighted MR imaging in 18 patients.

STUDY DESIGN: Only few studies have been published about diffusion-weighted imaging (DWI) within 24 h of traumatic spinal cord injury (tSCI). OBJECTIVES: The purpose of this study was to compare the imaging findings from conventional magnetic resonance imaging (MRI) and DWI in seven tSCI patients with findings in the existing literature. METHODS: Seven patients with tSCI at neurologic levels C2-T10 were examined with conventional MRI and DWI within 24 h post-injury. DWI was obtained with a b-factor of 1000 s mm(-2). American Spinal Injury Association (ASIA) scores and Spinal Cord Independence Measurement (SCIM) II item 12 after 12 months were collected. In addition, MEDLINE was searched from 1995 to 2010 to identify clinical tSCI studies reporting on MRI, DWI and apparent diffusion coefficient maps within 24 h post-injury to perform a meta-analysis. Images obtained with a b-factor of 1000 s mm(-2) were compared with lower b-factors. Differences were calculated using χ (2) tests. RESULTS: No associations were identified between the images of the seven tSCI patients and ASIA or SCIM II scores. Eighteen SCI patients (11 from the retrieved publications) were included in the meta-analysis. The detection rates of hyperintense signals on T2-weighted and DW imaging did not show significant differences at 94 and 72%, respectively. In addition, there were no significant differences in detection rates or diffusion abnormalities between subjects in whom DW images were obtained with a maximum b-factor of 1000 or <1000 s mm(-2). CONCLUSION: Our analysis suggests that T2-weighted and DW imaging have comparable detection rates for spinal cord damage in tSCI patients within 24 h post-injury.

The new World Health Organization Classification of Central Nervous System Tumors: what can the neuroradiologist really say?

The WHO Classification of Tumors of the Central Nervous System has become the worldwide standard for classifying and grading brain neoplasms. The most recent edition (WHO 2007) introduced a number of significant changes that include both additions and redefinitions or clarifications of existing entities. Eight new neoplasms and 4 new variants were introduced. This article reviews these entities, summarizing both their histology and imaging appearance. Now with more than 3 years of clinical experience following publication of the newest revision, we also ask, "What can the neuroradiologist really say?" Are there imaging findings that could suggest the preoperative diagnosis of a new tumor entity or variant?

Intracranial infections: clinical and imaging characteristics.

The radiologist plays a crucial role in identifying and narrowing the differential diagnosis of intracranial infections. A thorough understanding of the intracranial compartment anatomy and characteristic imaging findings of specific pathogens, as well incorporation of the clinical information, is essential to establish correct diagnosis. Specific types of infections have certain propensities for different anatomical regions within the brain. In addition, the imaging findings must be placed in the context of the clinical setting, particularly in immunocompromised and human immunodeficiency virus (HIV)-positive patients. This paper describes and depicts infections within the different compartments of the brain. Pathology-proven infectious cases are presented in both immunocompetent and immunocompromised patients, with a discussion of the characteristic findings of each pathogen. Magnetic resonance spectroscopy (MRS) characteristics for several infections are also discussed.

Imaging characteristics of toxoplasmosis encephalitis after bone marrow transplantation: report of two cases and review of the literature.

Toxoplasmosis encephalitis is a severe, but often misdiagnosed complication in patients after bone marrow transplantation (BMT). We describe the unique computed tomography (CT) and magnetic resonance (MR) imaging features of cerebral toxoplasmosis in two bone marrow recipients and compare them to the cases in the literature. To our knowledge, this is the first report analyzing the appearance of cerebral toxoplasmosis on diffusion-weighted MR imaging (DWI).

Malignant lymphoma of the cranial vault in an HIV-positive patient: imaging findings.

We describe the CT and MR imaging findings in an HIV-positive patient with malignant non-Hodgkin's lymphoma of the cranial vault, a rare site for lymphoma involvement. Autopsy revealed lymphomatous bone lesions, lymphoma in the epidural space, and a large necrotic lymphoma in the soft tissue of the skull.

Peripancreatic fat necrosis mimicking pancreatic cancer.

A case of peripancreatic fat necrosis, after an episode of acute pancreatitis, which mimicked pancreatic cancer with lymph node metastases, is presented. We describe the imaging findings with helical CT scanning and with unenhanced and mangafodipir-enhanced MR imaging, with special emphasis on the differential diagnoses.

Mannosylated lipoarabinomannans inhibit IL-12 production by human dendritic cells: evidence for a negative signal delivered through the mannose receptor.

IL-12 is a key cytokine in directing the development of type 1 Th cells, which are critical to eradicate intracellular pathogens such as Mycobacterium tuberculosis. Here, we report that mannose-capped lipoarabinomannans (ManLAMs) from Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium tuberculosis inhibited, in a dose-dependent manner, the LPS-induced IL-12 production by human dendritic cells. The inhibitory activity was abolished by the loss of the mannose caps or the GPI acyl residues. Mannan, which is a ligand for the mannose receptor (MR) as well as an mAb specific for the MR, also inhibited the LPS-induced IL-12 production by dendritic cells. Our results indicate that ManLAMs may act as virulence factors that contribute to the persistence of M. bovis bacillus Calmette-Guérin and M. tuberculosis within phagocytic cells by suppressing IL-12 responses. Our data also suggest that engagement of the MR by ManLAMs delivers a negative signal that interferes with the LPS-induced positive signals delivered by the Toll-like receptors.

Initial and follow-up MR imaging findings in AIDS-related progressive multifocal leukoencephalopathy treated with highly active antiretroviral therapy.

BACKGROUND AND PURPOSE: Recent studies have shown the beneficial effect of highly active antiretroviral therapy (HAART) in AIDS-related progressive multifocal leukoencephalopathy (PML). The purpose of our study was to evaluate the initial and follow-up imaging findings and survival in patients with PML who were treated with HAART. METHODS: The clinical course and MR imaging findings on initial and follow-up MR studies in four consecutive AIDS patients with PML who were treated with HAART are described. RESULTS: Two patients were short-term survivors and died after 3 months. Two patients are still alive, with a survival time of 22 and 43 months, respectively. On initial MR studies, more extensive white matter changes were seen in the short-term survivors. Development of a mass effect and temporary enhancement (in one patient) was observed in two HAART responders on follow-up MR studies. Increased hypointensity on T1-weighted images with concomitant low signal on fluid-attenuated inversion-recovery fast spin-echo (FLAIR-FSE) images was seen in two responders, representing leukomalacia. Atrophic changes of the involved areas of the brain, consistent with burnt out PML lesions, were seen in two long-term survivors. In the short-term survivors, increased hypointensity was present on T1-weighted images with increased high signal on FLAIR-FSE images, representing progressive destructive disease. CONCLUSION: Our results suggest that a clinical and radiologic response can be seen in some patients with AIDS-associated PML on HAART while in others there may be no beneficial response. Development of a mass effect and temporary enhancement on MR images in the early phase of treatment might represent positive predictive factors for prolonged survival.

Expression and immunogenicity of oncofetal antigen-immature laminin receptor in human renal cell carcinoma.

PURPOSE: The 32 to 44 kDa. oncofetal antigen-immature laminin receptor (OFA-iLR) is a multifunctional protein expressed by various tumors, including breast, lung, ovary and prostate carcinoma as well as lymphoma. OFA-iLR has been implicated in tumor invasiveness, metastasis and growth. Interferon-gamma producing effector T cells and interleukin (IL)-10 producing suppressor T cells specific for OFA-iLR have been described. MATERIALS AND METHODS: The 43515 IgG2a anti-OFA-iLR monoclonal antibody was used to detect OFA-iLR expression in human renal cell carcinoma tissue by flow cytometry and immunoblotting. Spontaneous or therapy induced immune responses against OFA-iLR were determined in patients with metastatic renal cell carcinoma. Proliferative and cytokine (interferon-gamma and IL-10) responses of peripheral blood mononuclear cells from patients with renal cell carcinoma against recombinant OFA-iLR were assessed. RESULTS: Using flow cytometry OFA-iLR was detected in all 13 tumors tested. Immunoblotting revealed differences in OFA-iLR expression in renal cell carcinoma and normal kidney tissue. OFA-iLR specific proliferative and cytokine responses of mononuclear cells were detected in all 6 patients tested. Importantly evidence was also obtained that treating metastatic renal cell carcinoma with tumor lysate pulsed dendritic cells would enhance OFA-iLR specific immunity. CONCLUSIONS: This study demonstrates that OFA-iLR is an immunogenic tumor associated antigen in human renal cell carcinoma. OFA-iLR specific effector T cells producing interferon-gamma may have a role in the control of tumor growth, whereas suppressor T cells producing IL-10 may promote tumor tolerance and, thus, tumor progression.

The disabled dendritic cell.

Dendritic cells are important antigen-presenting cells of the immune system that induce and modulate immune responses. They interact with T and B lymphocytes as well as with natural killer cells to promote activation and differentiation of these cells. Dendritic cells generated in vitro from monocytes by use of the cytokines GM-CSF and IL-4 are increasingly used clinically to enhance antitumor immunity in cancer patients. However, recent studies revealed that the functional repertoire of monocyte-derived dendritic cells may be incomplete. Important functions of monocyte-derived dendritic cells such as migration or the ability to induce natural killer cell activation or type 2 T helper cell differentiation appear to be impaired. We propose that all these deficiencies relate to a single biochemical deficiency of monocyte-derived dendritic cells. IL-4, which is used to generate monocyte-derived dendritic cells, suppresses phospholipase A2, the enzyme that liberates arachidonic acid from membrane phospholipids and contributes to the synthesis of platelet-activating factor. Monocyte-derived dendritic cells must therefore fail to generate platelet-activating factor as well as arachidonic acid derivatives such as prostaglandins, leukotrienes, and lipoxins, collectively referred to as eicosanoids. Since eicosanoids and platelet-activating factor are known to play an important role in processes such as leukocyte migration, natural killer cell activation, and type 2 T helper cell differentiation, the deficiency in eicosanoid and platelet-activating factor biosynthesis may be responsible for the observed handicaps of monocyte-derived dendritic cells.

Primary central nervous system lymphoma in AIDS: a wider spectrum of CT and MRI findings.

Diagnosis of primary central nervous system lymphoma (PCNSL) in patients with AIDS based on radiological findings is still a challenging problem. Our purpose was to review the CT and MRI findings in PCNSL in our patients with AIDS and compare them with those reported in the literature. CT and MRI of 28 patients with AIDS and pathologically confirmed PCNSL were analysed retrospectively for the number of lesions, their site, size, density, signal intensity, contrast enhancement, oedema and mass effect. We found 82 lesions. On CT 45 lesions were found in 22 patients, whereas MRI revealed 66 in 20 patients. The lymphoma was solitary in 20 patients (29 %) and multiple in 20 (71%). Spontaneous haemorrhage was seen in 7 patients. Contrast-enhanced MRI showed no enhancement in 27.3 % (18/66) of the lesions. In one patient diffuse signal abnormalities in the white matter were seen on T2-weighted images. Our findings suggest that the previously described spectrum imaging characteristics of PCNSL has widened. Neuroradiologists should be aware of the variable appearance in patients with AIDS. Spontaneous haemorrhage, a non-enhancing lesion, or diffuse white matter changes do not exclude lymphoma in an immunocompromised patient.

A clinically approved oral vaccine against pneumotropic bacteria induces the terminal maturation of CD83+ immunostimulatory dendritic cells.

Dendritic cells (DCs) are important antigen-presenting cells of the immune system that have attracted interest as cellular adjuvants to induce immunity in clinical settings. We have investigated the effects of Broncho-Vaxom, an oral vaccine composed of lysates from eight pneumotropic bacteria, on human monocyte-derived dendritic cells (moDCs). Broncho-Vaxom induced the terminal maturation of CD83+ moDCs. MoDCs stimulated with Broncho-Vaxom displayed a phenotype of activated DCs with high levels of major histocompatibility complex (MHC) molecules and increased levels of adhesion and co-stimulatory molecules. In addition, moDCs activated with Broncho-Vaxom exhibited enhanced T cell-stimulatory capacity in the allogeneic mixed leukocyte reaction. Broncho-Vaxom at 100 microg/ml was as potent as TNF-alpha at 1000 U/ml in activating human moDCs. Neither LPS-like activity nor bacterial DNA was found to be responsible for the maturation-inducing activity of Broncho-Vaxom, suggesting that Broncho-Vaxom contains other bacterial factors that are capable of inducing the terminal maturation of moDCs. In DC-based immunotherapy, Broncho-Vaxom could be used as a stimulus of DC maturation, which meets the standards of good manufacturing practice (GMP). In addition, vaccination with Broncho-Vaxom-loaded moDCs may be an attractive treatment option in preventing recurrent airway infection in predisposed individuals.

Effects of alpha1-adrenoceptor antagonists on cultured prostatic smooth muscle cells.

BACKGROUND: alpha1-adrenoceptor (alpha1-AR) antagonists, used to relieve the lower tract urinary symptoms (LUTS) in benign prostate hyperplasia (BPH) patients, are thought to act in inhibiting the contraction of stromal smooth muscle. An attempt was made using new technology to visualize and quantify the effect of alpha1-AR antagonists in a cell culture model of prostatic smooth muscle cells (SMC). METHODS: Prostatic smooth muscle cells cultured from human prostate tissue were treated with alpha1-AR agonists and antagonists. The effects on cell growth, cell contraction, differentiation status, and apoptosis were determined by means of an MTT cell viability assay, time-lapse video microscopy, RT-PCR analysis, and FACS analysis of annexin V/propidium iodide-stained cells, respectively. RESULTS: Prostatic smooth muscle cells derived from prostate tissue expressed SMC-specific markers. They showed spontaneous contractions, and phenylephrine increased the percentage of contracting cells by 3-fold. alpha1-AR antagonists inhibited spontaneous as well as phenylephrine-induced contractions. Long-term treatment with doxazosin induced differentiation tended towards a contractile phenotype, as indicated by an increase of the ratio of smooth muscle heavy chain myosin subtypes SM2/SM1. There was, however, no effect on cell growth. High concentrations of antagonist (100 microM) induced apoptosis in about 80% of the treated SMC. This effect was not cell-type-specific and was also seen in skin fibroblasts and immortalized prostate epithelial cells. CONCLUSION: In an easy-to-handle cell culture model of prostatic smooth muscle cells, the effects of alpha1-AR antagonists on cell contraction, growth, and differentiation can be investigated. The results indicate that in addition to inhibition of cell contraction, alpha1-AR antagonists have the potential to induce apoptosis.