Twofold improved tumor-to-brain contrast using a novel T1 relaxation-enhanced steady-state (T1RESS) MRI technique.

A technique that provides more accurate cancer detection would be of great value. Toward this end, we developed T1 relaxation-enhanced steady-state (T1RESS), a novel magnetic resonance imaging (MRI) pulse sequence that enables the flexible modulation of T1 weighting and provides the unique feature that intravascular signals can be toggled on and off in contrast-enhanced scans. T1RESS makes it possible to effectively use an MRI technique with improved signal-to-noise ratio efficiency for cancer imaging. In a proof-of-concept study, "dark blood" unbalanced T1RESS provided a twofold improvement in tumor-to-brain contrast compared with standard techniques, whereas balanced T1RESS greatly enhanced vascular detail. In conclusion, T1RESS represents a new MRI technique with substantial potential value for cancer imaging, along with a broad range of other clinical applications.

Non-Contrast-Enhanced Carotid MRA: Clinical Evaluation of a Novel Ungated Radial Quiescent-Interval Slice-Selective MRA at 1.5T.

BACKGROUND AND PURPOSE: Non-contrast-enhanced MRA techniques have experienced a renaissance due to the known correlation between the use of gadolinium-based contrast agents and the development of nephrogenic systemic fibrosis and the deposition of gadolinium in some brain regions. The purpose of this study was to assess the diagnostic performance of ungated non-contrast-enhanced radial quiescent-interval slice-selective MRA of the extracranial supra-aortic arteries in comparison with conventional contrast-enhanced MRA in patients with clinical suspicion of carotid stenosis. MATERIALS AND METHODS: In this prospective study, both MRA pulse sequences were performed in 31 consecutive patients (median age, 68.8 years; 19 men). For the evaluation, the cervical arterial system was divided into 35 segments (right and left side). Three blinded reviewers separately evaluated these segments. An ordinal scoring system was used to assess the image quality of arterial segments and the stenosis grading of carotid arteries. RESULTS: Overall venous contamination in quiescent-interval slice-selective MRA was rated as "none" by all readers in 84.9% of cases and in 8.1% of cases in contrast-enhanced MRA (P < .0001). The visualization quality of arterial segments was considered good to excellent in 40.2% for the quiescent-interval slice-selective MRA and in 52.2% for the contrast-enhanced MRA (P < .0001). The diagnostic accuracy of ungated quiescent-interval slice-selective MRA concerning the stenosis grading showed a total sensitivity and specificity of 85.7% and 90.0%, respectively. CONCLUSIONS: Ungated quiescent-interval slice-selective MRA can be used clinically as an alternative to contrast-enhanced MRA without a significantly different image quality or diagnostic accuracy for the detection of carotid stenosis at 1.5T.

Advances in non-contrast quiescent-interval slice-selective (QISS) magnetic resonance angiography.

There is a pressing clinical need to develop accurate, efficient non-contrast magnetic resonance angiography (NC-MRA) techniques. Our efforts in the field have focused on a novel non-subtractive technique called quiescent-interval slice-selective (QISS) MRA. Compared with other NC-MRA techniques, QISS has the advantage of being more accurate while enabling a simpler and more efficient workflow. The original implementation, which uses electrocardiogram (ECG) gating and a Cartesian k-space trajectory, is a reliable technique for the evaluation of peripheral arterial disease (PAD). Recent advances in QISS technology include the use of a radial k-space trajectory, which facilitates rapid imaging of the coronary, renal, and pulmonary arteries as well as other vascular beds, and ungated ("UnQISS") acquisitions for PAD.

In Silico analysis of stent deployment- effect of stent design.

Coronary artery disease (CAD) remains the leading cause of death in Europe and worldwide. One of the most common pathologic processes involved in CAD is atherosclerosis. Coronary stents are expandable scaffolds that are used to widen the occluded arteries and enable the blood flow restoration. To achieve an adequate delivery and placement of coronary stents different parameters play a significant role. Due to the strain that the stents are exposed to and the forces they should withstand, the stent design is dominant. This study focuses on investigating the effect of the stent design in two finite element models using two stents with difference in the strut thickness. The in silico deployment is performed in a reconstructed patient specific arterial segment. The results are analyzed in terms of stress in the stent and the arterial wall and demonstrate how stent expansion is extensively affected by the scaffold's design.

Carbapenem-resistant Enterobacteriaceae colonization and infection in critically ill patients: a retrospective matched cohort comparison with non-carriers.

OBJECTIVES: To examine whether carbapenem-resistant Enterobacteriaceae (CRE) carriage is associated with incidence of clinical infection as a means of assessing whether the morbidity and mortality associated with these bacteria are mediated by underlying conditions or intrinsic properties of CRE. METHODS: This retrospective matched cohort study compared the incidence of invasive infections in CRE-colonized patients and matched non-carriers in the intensive care unit (ICU). The primary outcome was infection caused by CRE of the same species as the colonizing strain among CRE carriers, and infections caused by carbapenem-sensitive strains of the same organism in non-carriers. Hospital discharge and death were considered as competing events. Competing-risks hazard analysis was performed for the entire cohort and for a nested cohort matched by Acute Physiology and Chronic Health Evaluation (APACHE) II scores, stratified by matching. RESULTS: In total, 146 CRE carriers were compared with 292 non-carriers. Patients were well matched for most risk factors for Enterobacteriaceae infection, including age, renal failure, previous invasive infection, previous hospitalization, APACHE II score, length of mechanical ventilation, length of hospitalization and CRE carriage. On regression analysis, colonization with CRE was independently associated with Enterobacteriaceae infection {cause-specific hazard ratio (CSHR) 2.06 [95% confidence interval (CI) 1.03-4.09]}. On regression analysis of the APACHE-II-matched cohort (N=284), colonization with CRE remained significantly associated with Enterobacteriaceae infection [CSHR 3.32 (95% CI 1.31-8.43)]. CONCLUSIONS: Colonization with CRE was associated with at least a two-fold increased risk of infection by the colonizing strain amongst ICU patients.

Quantitative Susceptibility Mapping in Cerebral Cavernous Malformations: Clinical Correlations.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been shown to assess iron content in cerebral cavernous malformations. In this study, our aim was to correlate lesional iron deposition assessed by quantitative susceptibility mapping with clinical and disease features in patients with cerebral cavernous malformations. MATERIALS AND METHODS: Patients underwent routine clinical scans in addition to quantitative susceptibility mapping on 3T systems. Data from 105 patients met the inclusion criteria. Cerebral cavernous malformation lesions identified on susceptibility maps were cross-verified by T2-weighted images and differentiated on the basis of prior overt hemorrhage. Mean susceptibility per cerebral cavernous malformation lesion (χ̄lesion) was measured to correlate with lesion volume, age at scanning, and hemorrhagic history. Temporal rates of change in χ̄lesion were evaluated in 33 patients. RESULTS: Average χ̄lesion per patient was positively correlated with patient age at scanning (P < .05, 4.1% change with each decade of life). Cerebral cavernous malformation lesions with prior overt hemorrhages exhibited higher χ̄lesion than those without (P < .05). Changes in χ̄lesion during 3- to 15-month follow-up were small in patients without new hemorrhage between the 2 scans (bias = -0.0003; 95% CI, -0.06-0.06). CONCLUSIONS: The study revealed a positive correlation between mean quantitative susceptibility mapping signal and patient age in cerebral cavernous malformation lesions, higher mean quantitative susceptibility mapping signal in hemorrhagic lesions, and minimum longitudinal quantitative susceptibility mapping signal change in clinically stable lesions. Quantitative susceptibility mapping has the potential to be a novel imaging biomarker supplementing conventional imaging in cerebral cavernous malformations. The clinical significance of such measures merits further study.

Quiescent-inflow single-shot magnetic resonance angiography using a highly undersampled radial k-space trajectory.

PURPOSE: We hypothesized that high undersampling factors could be used in conjunction with radial quiescent-inflow single-shot magnetic resonance angiography (MRA) to accelerate the data acquisition and enable multislice acquisitions. METHODS: Seven subjects were imaged on a 1.5 T MRI system. For multislice quiescent-inflow single-shot MRA, the venous saturation radiofrequency pulse, in-plane saturation radiofrequency pulse, and quiescent interval were applied only once before the first slice. RESULTS: The mean (standard deviation) measurements for the intra-arterial signal-to-noise ratio were as follows: Cartesian 1 slice-29.3 (5.5); radial 1 slice, 92 views-22.3 (3.6); radial 1 slice, 46 views-18.5 (2.0); radial 2 slices, 46 views-18.3 (3.2); and radial 3 slices, 32 views-21.7 (3.9), normalized for pixel size to 15.8. Horizontal striping was present with multislice radial quiescent-inflow single-shot MRA (especially with the three-slice acquisition) due to variable T1 relaxation between the concurrently acquired slices, but the image quality remained diagnostic. Vascular pathology in patients with peripheral arterial disease was well shown by all techniques. CONCLUSION: Very high undersampling factors in excess of 18 have been demonstrated for nonenhanced MRA using a radial quiescent-inflow single-shot technique, enabling the acquisition of two to three slices per cardiac cycle. Scan time for a complete peripheral MRA could be shortened to 2 min or less.

Live attenuated malaria vaccine designed to protect through hepatic CD8⁺ T cell immunity.

Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.

Evidence-based guideline: The role of diffusion and perfusion MRI for the diagnosis of acute ischemic stroke: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess the evidence for the use of diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) in the diagnosis of patients with acute ischemic stroke. METHODS: We systematically analyzed the literature from 1966 to January 2008 to address the diagnostic and prognostic value of DWI and PWI. RESULTS AND RECOMMENDATIONS: DWI is established as useful and should be considered more useful than noncontrast CT for the diagnosis of acute ischemic stroke within 12 hours of symptom onset. DWI should be performed for the most accurate diagnosis of acute ischemic stroke (Level A); however, the sensitivity of DWI for the diagnosis of ischemic stroke in a general sample of patients with possible acute stroke is not perfect. The diagnostic accuracy of DWI in evaluating cerebral hemorrhage is outside the scope of this guideline. On the basis of Class II and III evidence, baseline DWI volumes probably predict baseline stroke severity in anterior territory stroke (Level B) but possibly do not in vertebrobasilar artery territory stroke (Level C). Baseline DWI lesion volumes probably predict (final) infarct volumes (Level B) and possibly predict early and late clinical outcome measures (Level C). Baseline PWI volumes predict to a lesser degree the baseline stroke severity compared with DWI (Level C). There is insufficient evidence to support or refute the value of PWI in diagnosing acute ischemic stroke (Level U).

Benign cardiac tumours: cardiac CT and MRI imaging appearances.

Primary benign cardiac tumours are rarely found in clinical practice and are generally evaluated with echocardiography. However, with the increasing usage of helical multislice CT, the initial detection and evaluation of these masses may be made by the radiologist during routine daily practice for other indications. The echocardiographic, CT and cardiac MRI appearances of various benign cardiac tumours and masses are described and illustrated in this review.

Whole brain and localized magnetization transfer measurements are associated with cognitive impairment in patients infected with human immunodeficiency virus.

BACKGROUND AND PURPOSE: Patients infected with human immunodeficiency virus (HIV) are susceptible to cognitive deterioration. This study investigated the utility of magnetization transfer (MT) imaging for quantification of brain tissue alterations associated with cognitive deficits in patients with HIV. MATERIALS AND METHODS: MT ratios (MTR) were derived for whole brain and for regions of interest (ROIs) in the basal ganglia and white matter in 11 HIV and 12 control subjects. Relationships with severity of cognitive impairment and specific neuropsychological deficits were also evaluated. RESULTS: MTR values for normalized whole brain histogram peak height, whole brain histogram mean, and all examined ROIs were reduced in the HIV subjects. Normalized histogram peak height and mean for whole brain, as well as means for the corpus callosum, basal ganglia, and frontal white matter (FWM), were significantly correlated with severity of cognitive impairment. MTR values for white matter regions (corpus callosum, FWM, and centrum semiovale) were correlated with specific cognitive deficits. CONCLUSION: Quantitative MTR measurements, determined for the whole brain and for vulnerable ROIs, are sensitive to neuropathologic changes associated with cognitive impairment in HIV-infected patients.

Monocyte chemoattractant protein-1 correlates with subcortical brain injury in HIV infection.

Various biomarkers have been suggested as associative or predictive of HIV-associated neurocognitive impairment. Plasma levels of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-alpha), and hematocrit were evaluated for relationships with diffusion tensor imaging measurements of centrum semiovale, caudate, and putamen. MCP-1 levels correlated with tissue status (mean diffusivity) in all examined regions. Plasma markers were also significantly correlated with anisotropy measurements in centrum semiovale (TNF-alpha) and putamen (hematocrit).

Bone marrow diffusion measures correlate with dementia severity in HIV patients.

BACKGROUND AND PURPOSE: Escalation in monocyte trafficking from the bone marrow into the brain may play a critical role in central nervous system injury and cognitive deterioration in patients with HIV infection. This study tested the hypothesis that the mean diffusivity is sensitive to marrow changes in HIV patients and that these quantitative imaging measurements correlate with the severity of dementia. METHODS: The mean diffusivity (MD), determined for clival and calvarial marrow regions, was compared in 11 HIV-infected patients and 9 control subjects. The imaging measurements were also evaluated for relationships with dementia severity and markers of disease progression (CD4 and viral load in plasma). RESULTS: The MD was significantly reduced in both clival and calvarial marrow in HIV-infected patients (P =.006). Diffusion measurements for clival (P =.02) and for calvarial (P =.03) regions were significantly correlated with the severity of dementia. CONCLUSION: The results of this investigation support the utility of diffusion strategies for monitoring the marrow and provide further evidence of a relationship between marrow status changes and neurologic progression in HIV patients.

Diffusion alterations in corpus callosum of patients with HIV.

BACKGROUND AND PURPOSE: Diffusion alterations have been identified in the corpus callosum and frontal white matter of patients infected with human immunodeficiency virus (HIV), though the relevance of these findings to cognitive deterioration has not yet been determined. This study tested the hypothesis that diffusion tensor imaging can detect tissue status alterations in these regions in cognitively impaired patients infected with HIV and the acquired measurements correlate with the severity of cognitive impairment. METHODS: Fractional anisotropy (FA) and mean diffusivity (MD) were determined for corpus callosum (genu and splenium) and frontal white matter (FWM). The DTI measurements were compared in 11 HIV and 11 control participants. Patterns of relationship were examined with cognitive status measures from concurrent neurologic and neuropsychologic evaluations. RESULTS: FA values for the splenium were significantly reduced in the patients infected with HIV and correlated with dementia severity and deficits in motor speed. MD values for the splenium were significantly increased in the patients infected with HIV and correlated with deficits in motor speed. FA measurements were also significantly correlated with performance on visual memory (genu), visuoconstruction (FWM), and verbal memory (FWM) tasks. CONCLUSION: Diffusion abnormalities were identified in the splenium of the corpus callosum in patients infected with HIV, and these alterations were associated with dementia severity and motor speed losses. In vivo assessment of callosal integrity by using quantitative neuroimaging may have potential utility as a marker of brain injury in patients infected with HIV.

Epidemiology of capsular and surface polysaccharide in Staphylococcus aureus infections complicated by bacteraemia.

Staphylococcus aureus is a leading cause of serious hospital- and community-acquired infections. The discovery of serologically distinct capsular polysaccharides on the surface of clinical isolates has allowed the development of vaccines and passive protective immunity. We have studied patient characteristics, infection characteristics and the surface and capsular polysaccharide serotype distribution in patients with S. aureus infections complicated by bacteraemia admitted to VA hospitals in Maryland between 1995 and 2000. Nine hundred and ninety-three blood cultures from 331 patients were positive for S. aureus. Thirty-eight percent of patients had diabetes, 11% had end-stage renal failure, and 23% were injection drug users. Forty-two percent of infections were caused by methicillin-resistant strains (MRSA), and 60% were acquired during hospitalization. Serotyping of the first available isolate per patient (N=234 isolates) using polyclonal antibodies showed three major phenotypes--42%, type 8 (T8) capsule; 50%, type 5 (T5) capsule; and 8%, 336 polysaccharide. MRSA isolates were significantly more likely to be T5 than methicillin-susceptible isolates (66% vs. 39%, P<0.001). The proportion of T5 MRSA increased significantly (years 1-2: 41%; years 3-4: 65%; years 5-6: 90%, P<0.001). This large sample of patients with serious S. aureus infection confirms that capsular polysaccharides T5 and T8 cause most human infections, and together with serotype 336, account for nearly all those with bacteraemia.

Disease burden in HIV-associated cognitive impairment: a study of whole-brain imaging measures.

OBJECTIVE: To study whole-brain MR measures derived from diffusion tensor imaging and magnetization transfer imaging (MTI) for the in vivo assessment of cumulative neuropathologic changes in HIV and to evaluate the quantitative imaging strategies with respect to cognitive status measures including the severity of dementia and the degree of impairment in specific cognitive domains including attention, memory, constructional abilities, and motor speed. METHODS: Quantitative whole-brain measurements, including fractional anisotropy (FA), apparent diffusion coefficient (ADC), and magnetization transfer ratio (MTR), were derived from histograms and compared in HIV and control participants. Relationships between the MR and cognitive status measures were examined. RESULTS: Whole-brain FA and MTR were reduced in patients with HIV and correlated with dementia severity. Whole-brain MTR and ADC were correlated with psychomotor deficits. Evaluation of relationships between the studied MR measures indicated a correlation between ADC and MTR; FA was not correlated with either ADC or MTR. CONCLUSIONS: Findings from this investigation support the use of quantitative whole-brain MR measures for evaluation of disease burden in HIV. Reductions in whole-brain fractional anisotropy and magnetization transfer ratio (MTR) distinguished HIV and control subjects, and these measures were associated with dementia severity. Relationships were identified between whole-brain MTR and apparent diffusion coefficient and psychomotor deficits. Combining these quantitative strategies in neuroimaging examinations may provide more comprehensive information concerning ongoing changes in the brains of HIV patients.

Active surveillance for respiratory virus infections in adults who have undergone bone marrow and peripheral blood stem cell transplantation.

Community-acquired respiratory virus (RV) infections are an important cause of disease in immunocompromised adults with cancer. To investigate the viral etiology, incidence, clinical presentation, and outcome of RV infections in an outpatient cohort of adult bone marrow or peripheral blood stem cell transplant (SCT) recipients, we monitored 62 outpatient volunteers from January 1 to April 30, 2001. A nasopharyngeal aspirate was collected from subjects when they reported new respiratory symptoms and tested for RV (influenza A, influenza B, human parainfluenza 1-3, adenovirus, and respiratory syncytial virus) by culture and reverse transcription polymerase chain reaction (RT-PCR) assay. Of 62 subjects enrolled, 27% had received allogeneic SCT and 45% were within 1 year of their transplant. In all, 35 participants (56%) reported 37 episodes of respiratory symptoms. Of the 37 specimens tested, five (14%) were positive for RV by culture and 20 (54%) were positive by RT-PCR. Only six patients with RV infections developed lower respiratory tract illnesses; these patients had received either autologous or allogeneic transplants and developed illnesses between 41 and 2666 days post transplant. Although RV infections were common in SCT outpatients during the RV season, most participants had upper respiratory tract infections, which resolved without the need for hospitalization.

Phase 1 studies of Walter Reed Army Institute of Research candidate attenuated dengue vaccines: selection of safe and immunogenic monovalent vaccines.

We describe the results of initial safety testing of 10 live-attenuated dengue virus (DENV) vaccine candidates modified by serial passage in primary dog kidney (PDK) cells at the Walter Reed Army Institute of Research. The Phase 1 studies, conducted in 65 volunteers, were designed to select an attenuated vaccine candidate for each DENV serotype. No recipient of the DENV candidate vaccines sustained serious injury or required treatment. Three vaccine candidates were associated with transient idiosyncratic reactions in one volunteer each, resulting in their withdrawal from further clinical development. Increasing PDK cell passage of DENV-1, DENV-2, and DENV-3 candidate vaccines increased attenuation for volunteers, yet also decreased infectivity and immunogenicity. This effect was less clear for DENV-4 candidate vaccines following 15 and 20 PDK cell passages. Only one passage level each of the tested DENV-2, -3, and -4 vaccine candidates was judged acceptably reactogenic and suitable for expanded clinical study. Subsequent studies with more recipients will further establish safety and immunogenicity of the four selected vaccine candidates: DENV-1 45AZ5 PDK 20, DENV-2 S16803 PDK 50, DENV-3 CH53489 PDK 20, and DENV-4 341750 PDK 20.

Atypical antibody responses in dengue vaccine recipients.

Eight of 69 (12%) healthy adult volunteers vaccinated with monovalent live-attenuated dengue virus (DENV) vaccine candidates had atypical antibody responses, with depressed IgM:IgG antibody ratios and induction of high-titer hemagglutination-inhibiting and neutralizing (NT) antibodies to all four DENV serotypes. These features suggested flavivirus exposure prior to DENV vaccination, yet no volunteer had a history of previous flavivirus infection, flavivirus vaccination, or antibody to flaviviruses evident before DENV vaccination. Moreover, production of antibody to DENV by atypical responders (AR) was not accelerated compared with antibody responses in the 61 flavivirus-naive responders (NR). Further evaluation revealed no differences in sex, age, race, DENV vaccine candidate received, or clinical signs and symptoms following vaccination between AR and NR. However, viremia was delayed at the onset in AR compared with NR. A comparative panel of all AR and five randomly selected NR found flavivirus cross-reactive antibody after vaccination only in AR. Unexpectedly, six of eight AR had NT antibodies to yellow fever virus (YFV) > 1:10 before vaccination while NR had none (P = 0.04). The AR also universally demonstrated YFV NT antibody titers > or = 1:160 after DENV vaccination, whereas four of five NR failed to seroconvert (P = 0.02). Yellow fever virus priming broadens the antibody response to monovalent DENV vaccination. The effect of flavivirus priming on the clinical and immunologic response to tetravalent DENV vaccine remains to be determined.

[Sports in children and adolescents]. / Le sport chez l'enfant et l'adolescent.

The current conditions in Belgium are paradoxical. Indeed, adequate measures are now in place to allow sports activities in a favorable environment: increase in leisure time, widespread availability of indoor and outdoor facilities. However, there has been a significant increase in obesity among young people as well as a gradual erosion in physical fitness of young Belgians. Therefore, physical activity is mandated, not only as a general personal health issue, but also as a public health issue. It should be encouraged, taking into account psychological and physiological growth parameters of teenagers.