Jani Saunavaara

Extensive abnormality of brain white matter integrity in pathological gambling.

Several magnetic resonance imaging (MRI) studies in substance use disorders have shown brain white matter integrity abnormalities, but there are no studies in pathological gambling, a form of behavioral addiction. Our objective was to investigate possible changes in regional brain gray and white matter volumes, and axonal white matter integrity in pathological gamblers compared to healthy controls. Twenty-four subjects (12 clinically diagnosed male pathological gamblers and 12 age-matched healthy male volunteers) underwent structural and diffusion weighted brain MRI scans, which were analyzed with voxel-based morphometry and tract based spatial statistics. In pathological gamblers, widespread lower white matter integrity (lower fractional anisotropy, higher mean diffusivity) was seen in multiple brain regions including the corpus callosum, the cingulum, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the anterior limb of internal capsule, the anterior thalamic radiation, the inferior longitudinal fascicle and the uncinate/inferior fronto-occipital fascicle. There were no volumetric differences in gray or white matter between pathological gamblers and controls. The results suggest that pathological gambling is associated with extensive lower integrity of several brain white matter tracts. The diffusion abnormality closely resembles previous findings in individuals with substance addictions.

Prospective evaluation of planar bone scintigraphy, SPECT, SPECT/CT, 18F-NaF PET/CT and whole body 1.5T MRI, including DWI, for the detection of bone metastases in high risk breast and prostate cancer patients: SKELETA clinical trial

Purpose. Detection of bone metastases in breast and prostate cancer patients remains a major clinical challenge. The aim of the current trial was to compare the diagnostic accuracy of 99mTc-hydroxymethane diphosphonate (99mTc-HDP) planar bone scintigraphy (BS), 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and whole body 1.5 Tesla magnetic resonance imaging (MRI), including diffusion weighted imaging, (wbMRI+DWI) for the detection of bone metastases in high risk breast and prostate cancer patients. Material and methods. Twenty-six breast and 27 prostate cancer patients at high risk of bone metastases underwent 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and wbMRI+DWI. Five independent reviewers interpreted each individual modality without the knowledge of other imaging findings. The final metastatic status was based on the consensus reading, clinical and imaging follow-up (minimal and maximal follow-up time was 6, and 32 months, respectively). The bone findings were compared on patient-, region-, and lesion-level. Results. 99mTc-HDP BS was false negative in four patients. In the region-based analysis, sensitivity values for 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT, and wbMRI+DWI were 62%, 74%, 85%, 93%, and 91%, respectively. The number of equivocal findings for 99mTc-HDP BS, 99mTc-HDP SPECT, 99mTc-HDP SPECT/CT, 18F-NaF PET/CT and wbMRI+DWI was 50, 44, 5, 6, and 4, respectively. Conclusion. wbMRI+DWI showed similar diagnostic accuracy to 18F-NaF PET/CT and outperformed 99mTc-HDP SPECT/CT, and 99mTc-HDP BS.

Effect of Inhaled Xenon on Cerebral White Matter Damage in Comatose Survivors of Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

IMPORTANCE Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland. One hundred ten comatose patients (aged 24-76 years) who had experienced out-of-hospital cardiac arrest were randomized. INTERVENTIONS Patients were randomly assigned to receive either inhaled xenon combined with hypothermia (33°C) for 24 hours (n = 55 in the xenon group) or hypothermia treatment alone (n = 55 in the control group). MAIN OUTCOMES AND MEASURES The primary end point was cerebral white matter damage as evaluated by fractional anisotropy from diffusion tensor MRI scheduled to be performed between 36 and 52 hours after cardiac arrest. Secondary end points included neurological outcome assessed using the modified Rankin Scale (score 0 [no symptoms] through 6 [death]) and mortality at 6 months. RESULTS Among the 110 randomized patients (mean age, 61.5 years; 80 men [72.7%]), all completed the study. There were MRI data from 97 patients (88.2%) a median of 53 hours (interquartile range [IQR], 47-64 hours) after cardiac arrest. The mean global fractional anisotropy values were 0.433 (SD, 0.028) in the xenon group and 0.419 (SD, 0.033) in the control group. The age-, sex-, and site-adjusted mean global fractional anisotropy value was 3.8% higher (95% CI, 1.1%-6.4%) in the xenon group (adjusted mean difference, 0.016 [95% CI, 0.005-0.027], P = .006). At 6 months, 75 patients (68.2%) were alive. Secondary end points at 6 months did not reveal statistically significant differences between the groups. In ordinal analysis of the modified Rankin Scale, the median (IQR) value was 1 (1-6) in the xenon group and 1 (0-6) in the control group (median difference, 0 [95% CI, 0-0]; P = .68). The 6-month mortality rate was 27.3% (15/55) in the xenon group and 34.5% (19/55) in the control group (adjusted hazard ratio, 0.49 [95% CI, 0.23-1.01]; P = .053). CONCLUSIONS AND RELEVANCE Among comatose survivors of out-of-hospital cardiac arrest, inhaled xenon combined with hypothermia compared with hypothermia alone resulted in less white matter damage as measured by fractional anisotropy of diffusion tensor MRI. However, there was no statistically significant difference in neurological outcomes or mortality at 6 months. These preliminary findings require further evaluation in an adequately powered clinical trial designed to assess clinical outcomes associated with inhaled xenon among survivors of out-of-hospital cardiac arrest. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00879892.

Measurement of brown adipose tissue mass using a novel dual-echo magnetic resonance imaging approach: A validation study

OBJECTIVE The aim of this study was to evaluate and validate magnetic resonance imaging (MRI) for the visualization and quantification of brown adipose tissue (BAT) in vivo in a rat model. We hypothesized that, based on differences in tissue water and lipid content, MRI could reliably differentiate between BAT and white adipose tissue (WAT) and could therefore be a possible alternative for (18)F-Fluorodeoxyglucose Positron Emission Tomography ((18)FDG-PET), the current gold standard for non-invasive BAT quantification. MATERIALS/METHODS Eleven rats were studied using both (18)FDG-PET/CT and MRI (1.5 T). A dual echo (in-and-out-of-phase) sequence was used, both with and without spectral presaturation inversion recovery (SPIR) fat suppression (DUAL-SPIR) to visualize BAT, after which all BAT was surgically excised. The BAT volume measurements obtained via (18)FDG-PET/CT and DUAL-SPIR MR were quantitatively compared with the histological findings. All study protocols were reviewed and approved by the local ethics committee. RESULTS The BAT mass measurements that were obtained using DUAL-SPIR MR subtraction images correlated better with the histological findings (P=0.017, R=0.89) than did the measurements obtained using (18)FDG-PET/CT (P=0.78, R=0.15), regardless of the BAT metabolic activation state. Additionally, the basic feasibility of the DUAL-SPIR method was demonstrated in three human pilot subjects. CONCLUSIONS This study demonstrates the potential for MRI to reliably detect and quantify BAT in vivo. MRI can provide information beyond that provided by (18)FDG-PET imaging, and its ability to detect BAT is independent of its metabolic activation state. Additionally, MRI is a low-cost alternative that does not require radiation.

Optimization of b‐value distribution for biexponential diffusion‐weighted MR imaging of normal prostate

To determine the optimal b‐value distribution for biexponential diffusion‐weighted imaging (DWI) of normal prostate using both a computer modeling approach and in vivo measurements.

Prebiopsy multiparametric 3T prostate MRI in patients with elevated PSA, normal digital rectal examination, and no previous biopsy.

To find the diagnostic accuracy of 3T multiparametric magnetic resonance imaging (mpMRI) and mpMRI targeted transrectal ultrasound (TRUS)‐guided biopsy using visual coregistration (TB) in patients with elevated prostate‐specific antigen (PSA), normal digital rectal examination, and no previous biopsy.

Hidden word learning capacity through orthography in aphasia.

The ability to learn to use new words is thought to depend on the integrity of the left dorsal temporo-frontal speech processing pathway. We tested this assumption in a chronic aphasic individual (AA) with an extensive left temporal lesion using a new-word learning paradigm. She exhibited severe phonological problems and Magnetic Resonance Imaging (MRI) suggested a complete disconnection of this left-sided white-matter pathway comprising the arcuate fasciculus (AF). Diffusion imaging tractography confirmed the disconnection of the direct segment and the posterior indirect segment of her left AF, essential components of the left dorsal speech processing pathway. Despite her left-hemispheric damage and moderate aphasia, AA learned to name and maintain the novel words in her active vocabulary on par with healthy controls up to 6 months after learning. This exceeds previous demonstrations of word learning ability in aphasia. Interestingly, AAs preserved word learning ability was modality-specific as it was observed exclusively for written words. Functional magnetic resonance imaging (fMRI) revealed that in contrast to normals, AA showed a significantly right-lateralized activation pattern in the temporal and parietal regions when engaged in reading. Moreover, learning of visually presented novel word-picture pairs also activated the right temporal lobe in AA. Both AA and the controls showed increased activation during learning of novel versus familiar word-picture pairs in the hippocampus, an area critical for associative learning. AAs structural and functional imaging results suggest that in a literate person, a right-hemispheric network can provide an effective alternative route for learning of novel active vocabulary. Importantly, AAs previously undetected word learning ability translated directly into therapy, as she could use written input also to successfully re-learn and maintain familiar words that she had lost due to her left hemisphere lesion.

Diffusion tensor imaging and brain volumetry in Fabry disease patients

IntroductionFabry disease is a rare lysosomal storage disorder leading to cellular accumulation of globotriaosylceramide, especially in blood vessels. It is associated with severe early onset cerebrovascular disease and kidney and heart failure. The purpose of this study was to reveal possible disturbances in white matter integrity in Fabry disease patients using voxelwise diffusion-tensor imaging (DTI) analysis.MethodsTwelve Fabry disease patients, along with 13 healthy controls, underwent DTI and structural MRI. Voxel-based analysis of the DTI data was performed to assess possible differences in DTI parameters between Fabry disease patients and healthy controls. A selective region of interest analysis was performed for healthy volunteers and Fabry disease patients having a mild burden of T2-hyperintense lesions. We also measured normalised brain tissue volumes and performed a voxel-based volume analysis for grey matter.ResultsVoxel-based analysis of DTI data showed areas of significantly reduced fractional anisotropy and increased mean diffusivity in patients with Fabry disease. Eight patients had a mild burden of white matter lesions on their T2 scans. Region of interest analysis on areas showing reduced fractional anisotropy in voxelwise analysis also revealed reduced fractional anisotropy values in this patient group compared to eight healthy volunteers. The brain volume analyses did not reveal significant differences between the Fabry disease patients and the controls.ConclusionThese findings suggest a microstructural damage in brain white matter of Fabry disease patients, which can be revealed before excessive white matter lesions load is visible on conventional MR scans.

Prognostic impact of pretransplant iron overload measured with magnetic resonance imaging on severe infections in allogeneic stem cell transplantation.

Infections and graft‐versus‐host disease (GVHD) are the main causes of transplant‐related mortality (TRM) of patients undergoing allo‐SCT. The role of iron overload (IO) has been debated in this context. Studies, performed with non‐specific surrogate markers of iron, suggest that IO predicts poor outcome after allo‐SCT.

Human Brown Adipose Tissue Temperature and Fat Fraction Are Related to Its Metabolic Activity

Background and Aim The metabolic activity of human brown adipose tissue (BAT) has been previously examined using positron emission tomography (PET). The aim of this study was to use proton magnetic resonance spectroscopy (1H MRS) to investigate whether the temperature and the fat fraction (FF) of BAT and white adipose tissue (WAT) are associated with BAT metabolic activity determined by deoxy-2-18F-fluoro-d-glucose (18F-FDG)-PET. Materials and Methods Ten healthy subjects (four women, six men; 25 to 45 years of age) were studied using PET-magnetic resonance imaging during acute cold exposure and at ambient room temperature. BAT and subcutaneous WAT 1H MRS were measured. The tissue temperature and the FF were derived from the spectra. Tissue metabolic activity was studied through glucose uptake using dynamic FDG PET scanning during cold exposure. A 2-hour hyperinsulinemic euglycemic clamp was performed on eight subjects. Results The metabolic activity of BAT associated directly with the heat production capacity and inversely with the FF of the tissue. In addition, the lipid-burning capacity of BAT associated with whole-body insulin sensitivity. During cold exposure, the FF of BAT was lower than at room temperature, and cold-induced FF of BAT associated inversely with high-density lipoprotein and directly with low-density lipoprotein cholesterol. Conclusion Both 1H MRS-derived temperature and FF are promising methods to study BAT activity noninvasively. The association between the lipid-burning capacity of BAT and whole-body insulin sensitivity emphasizes the role of BAT in glucose handling. Furthermore, the relation of FF to high-density lipoprotein and low-density lipoprotein cholesterol suggests that BAT has a role in lipid clearance, thus protecting tissues from excess lipid load.