18F-Flortaucipir in TDP-43 associated frontotemporal dementia.

Retention of 18F-Flortaucipir is reportedly increased in the semantic variant of primary progressive aphasia (svPPA), which is dominated by TDP-43 pathology. However, it is unclear if 18F-Flortaucipir is also increased in other TDP-43 diseases, such as bvFTD caused by a C9orf72 gene mutation. We therefore recruited six C9orf72 expansion carriers, six svPPA patients, and 54 healthy controls. All underwent 18F-Flortaucipir PET and MRI scanning. Data from 39 Alzheimer's Disease patients were used for comparison. PET tracer retention was assessed both at the region-of-interest (ROI) and at the voxel-level. Further, autoradiography using 3H-Flortaucipir was performed. SvPPA patients exhibited higher 18F-Flortaucipir retention in the lateral temporal cortex bilaterally according to ROI- and voxel-based analyses. In C9orf72 patients, 18F-Flortaucipir binding was slightly increased in the inferior frontal lobes in the ROI based analysis, but these results were not replicated in the voxel-based analysis. Autoradiography did not show specific binding in svPPA cases or in C9orf72-mutation carriers. In conclusion, temporal lobe 18F-Flortaucipir retention was observed in some cases of svPPA, but the uptake was of a lower magnitude compared to AD dementia. C9orf72-mutation carriers exhibited none or limited 18F-Flortaucipir retention, indicating that 18F-Flortaucipir binding in TDP-43 proteinopathies is not a general TDP-43 related phenomenon.

Arterial Spin-Labeling in Children with Brain Tumor: A Meta-Analysis.

BACKGROUND: The value of arterial spin-labeling in a pediatric population has not been assessed in a meta-analysis. PURPOSE: Our aim was to assess the diagnostic accuracy of arterial spin-labeling-derived cerebral blood flow to discriminate low- and high-grade tumors. DATA SOURCES: MEDLINE, EMBASE, the Web of Science Core Collection, and the Cochrane Library were used. STUDY SELECTION: Pediatric patients with arterial spin-labeling MR imaging with verified neuropathologic diagnoses were included. DATA ANALYSIS: Relative CBF and absolute CBF and tumor grade were extracted, including sequence-specific information. Mean differences in CBF between low- and high-grade tumors were calculated. Study quality was assessed. DATA SYNTHESIS: Data were aggregated using the bivariate summary receiver operating characteristic curve model. Heterogeneity was explored with meta-regression and subgroup analyses. The study protocol was published at PROSPERO (CRD42017075055). Eight studies encompassing 286 pediatric patients were included. The mean differences in absolute CBF were 29.62 mL/min/100 g (95% CI, 10.43-48.82 mL/min/100 g), I2 = 74, P = .002, and 1.34 mL/min/100 g (95% CI, 0.95-1.74 mL/min/100 g), P < .001, I2 = 38 for relative CBF. Pooled sensitivity for relative CBF ranged from 0.75 to 0.90, and specificity, from 0.77 to 0.92 with an area under curve = 0.92. Meta-regression showed no moderating effect of sequence parameters TE, TR, acquisition time, or ROI method. LIMITATIONS: Included tumor types, analysis method, and original data varied among included studies. CONCLUSIONS: Arterial spin-labeling-derived CBF measures showed high diagnostic accuracy for discriminating low- and high-grade tumors in pediatric patients with brain tumors. The relative CBF showed less variation among studies than the absolute CBF.

White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus.

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma.

CONTEXT: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. OBJECTIVE: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. DESIGN: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. SETTING: The South Medical Region of Sweden (2.5 million inhabitants). PARTICIPANTS: Included were 41 patients (24 women, ≥17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HL was found in 23 patients. MAIN OUTCOME MEASURES: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. RESULTS: Right uncinate fasciculus was significantly altered (P ≤ 0.01). Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. CONCLUSIONS: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.

MRI of the Swallow Tail Sign: A Useful Marker in the Diagnosis of Lewy Body Dementia?

BACKGROUND AND PURPOSE: There are, to date, no MR imaging diagnostic markers for Lewy body dementia. Nigrosome 1, containing dopaminergic cells, in the substantia nigra pars compacta is hyperintense on SWI and has been called the swallow tail sign, disappearing with Parkinson disease. We aimed to study the swallow tail sign and its clinical applicability in Lewy body dementia and hypothesized that the sign would be likewise applicable in Lewy body dementia. MATERIALS AND METHODS: This was a retrospective cross-sectional multicenter study including 97 patients (mean age, 65 ± 10 years; 46% women), consisting of the following: controls (n = 21) and those with Lewy body dementia (n = 19), Alzheimer disease (n = 20), frontotemporal lobe dementia (n = 20), and mild cognitive impairment (n = 17). All patients underwent brain MR imaging, with susceptibility-weighted imaging at 1.5T (n = 46) and 3T (n = 51). The swallow tail sign was assessed independently by 2 neuroradiologists. RESULTS: Interrater agreement was moderate (κ = 0.4) between raters. An abnormal swallow tail sign was most common in Lewy body dementia (63%; 95% CI, 41%-85%; P < .001) and had a predictive value only in Lewy body dementia with an odds ratio of 9 (95% CI, 3-28; P < .001). The consensus rating for Lewy body dementia showed a sensitivity of 63%, a specificity of 79%, a negative predictive value of 89%, and an accuracy of 76%; values were higher on 3T compared with 1.5T. The usefulness of the swallow tail sign was rater-dependent with the highest sensitivity equaling 100%. CONCLUSIONS: The swallow tail sign has diagnostic potential in Lewy body dementia and may be a complement in the diagnostic work-up of this condition.

Proximity of brain infarcts to regions of endogenous neurogenesis and involvement of striatum in ischaemic stroke.

BACKGROUND AND PURPOSE: Clinical stroke trials with stem cell-based approaches aiming for trophic actions, modulation of inflammation and neuroprotection are ongoing. However, experimental studies also suggest that neuronal replacement by grafted neural stem cells (NSCs) and possibly by endogenous NSCs from the subventricular zone (SVZ) may restore function in the stroke-damaged striatum. To evaluate the potential clinical impact of these findings, we analyzed the spatial relationship of infarcts to the SVZ and the proportion of individuals with striatal lesions in a consecutive series of ischaemic stroke patients. METHODS: Patients aged 20-75 years with first-ever ischaemic stroke underwent DW-MRI of the brain within 4 days after stroke onset. We analyzed location, size, number of acute focal ischaemic abnormalities and their spatial relationship to the SVZ. Stroke severity was assessed using NIH Stroke Scale (NIHSS). RESULTS: Of 108 included patients, the distance from the nearest margin of the infarct(s) to the SVZ was ≤2 mm in 51/102 patients with visible ischaemic lesions on DW-MRI. Twenty-four patients had involvement of striatum. Eight of these had predominantly striatal lesions, that is >50% of the total ischaemic lesion volume was located in caudate nucleus and/or putamen. These 8 patients had a median NIHSS of 3. CONCLUSIONS: Many stroke patients have infarcts located close to the SVZ, providing some supportive evidence that optimized endogenous neurogenesis may have therapeutic potential. However, predominantly striatal infarcts are rare and tend to give mild neurological deficits, indicating that striatum should not be the primary target for neuronal replacement efforts in humans.

Radiation dose reduction in CT of the brain: can advanced noise filtering compensate for loss of image quality?

BACKGROUND: Computed tomography (CT) of the brain is performed with high local doses due to high demands on low contrast resolution. Advanced algorithms for noise reduction might be able to preserve critical image information when reducing radiation dose. PURPOSE: To evaluate the effect of advanced noise filtering on image quality in brain CT acquired with reduced radiation dose. MATERIAL AND METHODS: Thirty patients referred for non-enhanced CT of the brain were examined with two helical protocols: normal dose (ND, CTDI(vol) 57 mGy) and low dose (LD, CTDI(vol) 40 mGy) implying a 30% radiation dose reduction. Images from the LD examinations were also postprocessed with a noise reduction software with non-linear filters (SharpView CT), creating filtered low dose images (FLD) for each patient. The three image stacks for each patient were presented side by side in randomized order. Five radiologists, blinded for dose level and filtering, ranked these three axial image stacks (ND, LD, FLD) as best to poorest (1 to 3) regarding three image quality criteria. Measurements of mean Hounsfield units (HU) and standard deviation (SD) of the HU were calculated for large region of interest in the centrum semiovale as a measure for noise. RESULTS: Ranking results in pooled data showed that the advanced noise filtering significantly improved the image quality in FLD as compared to LD images for all tested criteria. No significant differences in image quality were found between ND examinations and FLD. However, there was a notable inter-reader spread of the ranking. SD values were 15% higher for LD as compared to ND and FLD. CONCLUSION: The advanced noise filtering clearly improves image quality of CT examinations of the brain. This effect can be used to significantly lower radiation dose.

Diffusion-weighted MRI measurements on stroke patients reveal water-exchange mechanisms in sub-acute ischaemic lesions.

The aim of this study was to investigate the diffusion time dependence of signal-versus-b curves obtained from diffusion-weighted magnetic resonance imaging (DW-MRI) of sub-acute ischaemic lesions in stroke patients. In this case series study, 16 patients with sub-acute ischaemic stroke were examined with DW-MRI using two different diffusion times (60 and 260 ms). Nine of these patients showed sufficiently large lesions without artefacts to merit further analysis. The signal-versus-b curves from the lesions were plotted and analysed using a two-compartment model including compartmental exchange. To validate the model and to aid the interpretation of the estimated model parameters, Monte Carlo simulations were performed. In eight cases, the plotted signal-versus-b curves, obtained from the lesions, showed a signal-curve split-up when data for the two diffusion times were compared, revealing effects of compartmental water exchange. For one of the patients, parametric maps were generated based on the extracted model parameters. These novel observations suggest that water exchange between different water pools is measurable and thus potentially useful for clinical assessment. The information can improve the understanding of the relationship between the DW-MRI signal intensity and the microstructural properties of the lesions.

Determining 'true' glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations.

OBJECTIVE: To determine 'true' glomerular filtration rate (GFR) in healthy adults as renal clearance following infusion of inulin, and compare that result with those obtained using other markers and clearance techniques and with estimations of GFR using creatinine-based prediction equations. MATERIAL AND METHODS: Twenty healthy volunteers (11 females) with a median age of 27 years (range 19-36 years) received bolus doses of inulin and iohexol i.v. and 16 blood samples were taken after injection. Then, inulin and iohexol were infused to give stable plasma concentrations and blood and urine samples were collected. Residual bladder volume was estimated using ultrasound scanning. Plasma and urine concentrations of inulin and iohexol were determined using chromatography and resorcinol methods, respectively. Different methods of GFR determination were compared as well as four formulae for GFR estimation based on serum creatinine. RESULTS: 'True' GFR, i.e. renal clearance of inulin during its infusion, was a median of 117 ml/min/1.73 m2 (inter-quartile range 106-129 ml/min/1.73 m2). Similar values of GFR were obtained with renal clearance of iohexol during its infusion and also with plasma (body) clearance of inulin or iohexol following bolus injections and using 16 or five plasma samples. Endogenous creatinine clearance was higher (p<0.001) than true GFR (median 23 ml/min/1.73 m2). Plasma clearance of iohexol and inulin based on their concentrations in four blood samples underestimated their renal clearance considerably. All four creatinine-based formulae markedly underestimated renal inulin clearance. CONCLUSIONS: Plasma and renal clearance of iohexol and inulin were similar in healthy adults. Underestimation of GFR was noted when plasma clearance of iohexol and inulin was based on four but not five or more blood samples. Some prediction equations underestimate true GFR to such an extent that caution must be taken when using them to evaluate normal or high GFR values.

Tumor extension in high-grade gliomas assessed with diffusion magnetic resonance imaging: values and lesion-to-brain ratios of apparent diffusion coefficient and fractional anisotropy.

PURPOSE: To determine whether the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) can distinguish tumor-infiltrated edema in gliomas from pure edema in meningiomas and metastases. MATERIAL AND METHODS: Thirty patients were studied: 18 WHO grade III or IV gliomas, 7 meningiomas, and 5 metastatic lesions. ADC and FA were determined from ROIs placed in peritumoral areas with T2-signal changes, adjacent normal appearing white matter (NAWM), and corresponding areas in the contralateral healthy brain. Values and lesion-to-brain ratios from gliomas were compared to those from meningiomas and metastases. RESULTS: Values and lesion-to-brain ratios of ADC and FA in peritumoral areas with T2-signal changes did not differ between gliomas, meningiomas, and metastases (P = 0.40, P = 0.40, P = 0.61, P = 0.34). Values of ADC and FA and the lesion-to-brain ratio of FA in the adjacent NAWM did not differ between tumor types (P = 0.74, P = 0.25, and P = 0.31). The lesion-to-brain ratio of ADC in the adjacent NAWM was higher in gliomas than in meningiomas and metastases (P = 0.004), but overlapped between tumor types. CONCLUSION: Values and lesion-to-brain ratios of ADC and FA in areas with T2-signal changes surrounding intracranial tumors and adjacent NAWM were not helpful for distinguishing pure edema from tumor-infiltrated edema when data from gliomas, meningiomas, and metastases were compared.

Functional magnetic resonance imaging at 3T as a clinical tool in patients with intracranial tumors.

PURPOSE: To investigate the potential of functional magnetic resonance imaging (fMRI) at 3T as a clinical tool in the preoperative evaluation of patients with intracranial tumors. High magnetic field strength such as 3T is of benefit for fMRI because signal-to-noise ratio and sensitivity to susceptibility changes are field-strength-dependent. MATERIAL AND METHODS: Twenty patients with tumors close to eloquent sensorimotor or language areas were studied. Motor, sensory, and two language paradigms (word generation, rhyming) were used; their effectiveness was determined as the percentage of patients in whom the functional area of interest was activated. Activation maps were calculated and their quality rated as high, adequate, or insufficient. The influence of fMRI on the neurosurgical decision regarding operability, surgical approach, and extent of the resection, was assessed. RESULTS: Paradigm effectiveness was 90% for motor and 95% for sensory stimulation, and varied from 79% to 95% for word generation and rhyming in combination. Ninety percent of the activation maps held high or adequate quality. fMRI proved useful: in the decision to operate (9 patients), in the surgical approach (13 patients), and in extent of the resection (12 patients). CONCLUSION: fMRI at 3T is a clinically applicable tool in the work-up of patients with intracranial tumors.

Biliary and total extrarenal clearance of inulin and iohexol in pigs. A source of error when determining gfr as body clearance.

Biliary clearance, total extrarenal clearance, body and renal clearance of inulin and iohexol were determined in 11 normal and 11 nephrectomized pigs. The biliary clearance of inulin, calculated as biliary excretion divided by the plasma concentration, was 0.04 and 0.01 ml min(-1) 10 kg(-1) and of iohexol 0.21 and 0.1 ml min(-1) 10 kg(-1), in normal, respectively, nephrectomized pigs (p < 0.05). The extrarenal clearance of inulin, calculated as body minus renal clearance, was 2.7 and 0.7 ml min(-1) 10 kg(-1) and of iohexol 3.7 and 0.7 ml min(-1) 10 kg(-1) in normal, respectively, nephrectomized pigs (p < 0.05). Some hours after injection of the markers their plasma concentrations were much higher in the nephrectomized pigs. This higher plasma concentration was not matched by an equally higher biliary excretion and therefore biliary clearance decreased. The smaller total extrarenal clearance in nephrectomized pigs, i.e. the overestimation of GFR when calculated as body clearance, indicates that this source of error decreases with decreasing renal function.

Ipsilateral multiple groin hernias.

BACKGROUND: Recurrence rates after surgical repair of groin hernia vary between 3% and 20%. One possible reason for recurrent hernias are ipsilateral multiple hernias, which might have been overlooked at the primary operation. METHODS: In the present series 1010 patients with unclear groin pain underwent herniography. RESULTS: A total of 314 patients had hernias, and seventy-one (23%) of these had multiple hernias. Ipsilateral multiple hernias were found in 18 (6%) patients. Ipsilateral multiple hernias were present in 9 (6%) of 144 patients with an indirect hernia, in 17 (12%) of 144 patients with a direct hernia, in 5 (21%) of 24 patients with a femoral hernia, and in 3 (23%) of 13 patients with an obturator hernia. The hernias were of indirect, direct, femoral, and obturator types. CONCLUSIONS: The frequency of ipsilateral multiple hernias is much higher than the frequency reported during herniorrhaphy. Such overlooked ipsilateral multiple groin hernias may account for some of the so-called recurrences after herniorrhaphy. Therefore a careful exploration of the groin is mandatory. Preoperative herniography may also prove to be useful in patients with recurrent groin symptoms after herniorrhaphy.

Solid bolus swallowing in the radiologic evaluation of dysphagia.

Patients with dysphagia, heartburn and chest pain are regularly referred for radiologic evaluation of swallowing. The liquid barium swallow has been of great value for the biphasic evaluation of the pharynx and esophagus. Though many patients complain of dysphagia specifically for solids, solid bolus swallow is usually not part of the evaluation. For the present study we therefore included the use of a solid bolus with a diameter of 13 mm and interviewed the patients carefully for any symptoms during this tablet swallow. Of 200 patients examined, the tablet passed through the esophagus without delay in 102. In the 98 patients with delayed passage, the solid bolus arrest occurred in the pharynx in 5 and in the esophagus in 93. Arrest in the esophagus was due to esophageal dysmotility in 48 patients. Twenty of these were symptomatic during the tablet swallow. A narrowing was the cause in 45, of whom 9 had symptoms. In 18 patients (9%) the solid bolus added key information to the radiologic evaluation. We therefore recommend that the solid bolus is included in the routine radiologic work-up of patients with dysphagia. Careful attention to symptoms during the tablet swallow is important.