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Objective: To describe the development, design and function of an innovative international clinical research network for neuroimaging research, based in Australia, within a joint state health service/medical school. This Australian, US, Scandinavian Imaging Exchange (AUSSIE) network focuses upon identifying neuroimaging biomarkers for neuropsychiatric and neurodegenerative disease. Methods: We describe a case study of the iterative development of the network, identifying characteristic features and methods which may serve as potential models for virtual clinical research networks. This network was established to analyse clinically-derived neuroimaging data relevant to neuropsychiatric and neurodegenerative disease, specifically in relation to subcortical brain structures. Results: The AUSSIE network has harnessed synergies from the individual expertise of the component groups, primarily clinical neuroscience researchers, to analyse a variety of clinical data. Conclusion: AUSSIE is an active virtual clinical research network, analogous to a connectome, which is embedded in health care and has produced significant research, advancing our understanding of neuropsychiatric and neurodegenerative disease through the lens of neuroimaging.

Background We describe the clinical characteristics of a Swedish family with autosomal dominant cerebellar ataxia, sensory and autonomic neuropathy, additional neurological features and unknown genetic cause. Methods Fourteen affected family members were identified. Their disorder was characterized by neurological examination, MRI, electroneurography, electromyography, MIBG-scintigraphy, and tilt-testing. Results The disorder presented as a balance and gait disturbance starting between 16 and 47 years of age. Cerebellar ataxia progressed slowly over the course of decades, and MRI showed mild to moderate cerebellar atrophy. Sensory axonal polyneuropathy was the most prominent additional feature and occurred in all patients examined. Autonomic neuropathy caused pronounced orthostatic dysregulation in at least four patients. Several affected members showed muscle wasting, and mild upper or lower motor neuron signs were documented. Patients had no nystagmus but slow or hypometric horizontal saccades and ocular motor apraxia. Cognition remained unimpaired, and there were no non-neurological disease manifestations. The disorder affected men and women in successive generations in a pattern compatible with autosomal dominant inheritance without evidence of anticipation. A second family where 7 members had very similar symptoms was identified and its origin traced back to the same village in southern Sweden as that of the first family's ancestors. All relevant known genetic causes of cerebellar ataxia were excluded by a novel next-generation sequencing approach. Conclusion We present two probably related Swedish families with a characteristic and novel clinical syndrome of cerebellar ataxia and sensory polyneuropathy. The study serves as a basis for the mapping of the underlying genetic cause.

Hyaluronic acid (HA) has been shown to affect angiogenesis and the function of the blood-brain barrier, and a crucial role for HA in atherosclerosis has been described. We have recently demonstrated changes in the levels of HA in cerebrospinal fluid (CSF) in patients with Alzheimer's disease (AD) with documented vascular alterations. To further investigate if the level of HA in CSF can be used as a clinical diagnostic biomarker to identify vascular pathology in dementia, we analyzed the levels of HA in the CSF of patients with vascular dementia (VaD) (n = 46), AD (n = 45), and controls without dementia (n = 26). In line with our previous data, we found significantly increased levels of HA in CSF from patients with VaD compared with controls, whereas the levels of HA in patients with AD were found to be unaltered compared with controls and patients with VaD. We also detected increased levels of HA in individuals with vascular changes determined as significant white matter changes or previous infarction on cranial computed tomography or magnetic resonance imaging, compared with individuals without these findings. Furthermore, we found a significant positive correlation between the levels of HA and the CSF/serum albumin ratio, an indicator of blood-brain barrier integrity, in patients with VaD and AD, supporting the role of HA in vascular changes in the brain. Our results indicate a potential diagnostic value for the detection of vascular brain changes in dementia using CSF levels of HA, but emphasize the importance of further development of more sensitive HA assays.

Dynamic susceptibility contrast MRI (DSC-MRI) tends to return elevated estimates of cerebral blood flow (CBF) and cerebral blood volume (CBV). In this study, subject-specific calibration factors (CFs), based on steady-state CBV measurements, were applied to rescale the absolute level of DSC-MRI CBF. Twenty healthy volunteers were scanned in a test–retest approach. Independent CBV measurements for calibration were accomplished using a T1-based contrast agent steady-state method (referred to as Bookend), as well as a blood-nulling vascular space occupancy (VASO) approach. Calibrated DSC-MRI was compared with pseudo-continuous arterial spin labeling (pCASL). For segmented grey matter (GM) regions of interests (ROIs), pCASL-based CBF was 63 ± 11 ml/(min 100 g) (mean ± SD). Nominal CBF from non-calibrated DSC-MRI was 277 ± 61 ml/(min 100 g), while calibrations resulted in 56 ± 23 ml/(min 100 g) (Bookend) and 52 ± 16 ml/(min 100 g) (VASO). Calibration tended to eliminate the overestimation, although the repeatability was generally moderate and the correlation between calibrated DSC-MRI and pCASL was low (r

To evaluate and mutually compare the tail-scaling approach and the prebolus administration concept for reduction of arterial partial volume effects (PVEs), because reproducible absolute quantification of cerebral blood flow (CBF) by dynamic susceptibility contrast magnetic resonance imaging (MRI) is often hampered by PVEs in the arterial input function (AIF) registration.Twenty healthy volunteers were scanned in a test-retest study with 7-20 days between investigations to examine the quantitative values and the repeatability of CBF estimates obtained from the tail-scaling and the prebolus administration approaches.Average grey matter CBF was 80 ± 18 mL/100 g/min (mean ± SD) using tail-scaling and 56 ± 18 mL/100 g/min using prebolus administration. The intraclass correlation coefficient was 0.52 for the tail-scaling approach and 0.86 for the prebolus administration concept.Both correction methods resulted in considerably reduced arterial PVEs, leading to quantitative estimates of perfusion approaching those typically obtained by other perfusion modalities. The CBF estimates obtained using the prebolus administration concept showed superior repeatability. Potential sources of uncertainty in the tail-scaling approach include the use of venous concentration curves influenced by PVEs or by geometric distortions (ie, vessel pixel shifts) in the steady-state period.

Arterial partial-volume effects (PVEs) often hamper reproducible absolute quantification of cerebral blood flow (CBF) and cerebral blood volume (CBV) obtained by dynamic susceptibility contrast MRI (DSC-MRI). The aim of this study was to examine whether arterial PVEs in DSC-MRI data can be minimized by rescaling the arterial input function (AIF) using a sagittal-sinus venous output function obtained following a prebolus administration of a low dose of contrast agent.The study was carried out as a test-retest experiment in 20 healthy volunteers to examine the repeatability of the CBF and CBV estimates. All subjects were scanned twice with 7-20 days between investigations.DSC-MRI returned an overestimated average whole-brain CBF of 220 ± 44 mL/100 g/min (mean ± SD) before correction and 44 ± 15 mL/100 g/min when applying the prebolus design, averaged over all scans. Average whole-brain CBV was 20 ± 2.0 mL/100 g before correction and 4.0 ± 1.0 mL/100 g after prebolus correction.Quantitative estimates of CBF and CBV, obtained with the proposed prebolus DSC-MRI technique, approached those typically obtained by other perfusion modalities. The CBF and CBV estimates showed good repeatability.

PurposeThe aim of the study was to determine the usefulness of diffusion tensor tractography (DTT) in parkinsonian disorders using a recently developed method for normalization of diffusion data and tract size along white matter tracts. Furthermore, the use of DTT in selected white matter tracts for differential diagnosis was assessed.MethodsWe quantified global and regional diffusion parameters in major white matter tracts in patients with multiple system atrophy (MSA), progressive nuclear palsy (PSP), idiopathic Parkinson's disease (IPD) and healthy controls). Diffusion tensor imaging data sets with whole brain coverage were acquired at 3 T using 48 diffusion encoding directions and a voxel size of 2×2×2 mm(3). DTT of the corpus callosum (CC), cingulum (CG), corticospinal tract (CST) and middle cerebellar peduncles (MCP) was performed using multiple regions of interest. Regional evaluation comprised projection of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and the apparent area coefficient (AAC) onto a calculated mean tract and extraction of their values along each structure.ResultsThere were significant changes of global DTT parameters in the CST (MSA and PSP), CC (PSP) and CG (PSP). Consistent tract-specific variations in DTT parameters could be seen along each tract in the different patient groups and controls. Regional analysis demonstrated significant changes in the anterior CC (MD, RD and FA), CST (MD) and CG (AAC) of patients with PSP compared to controls. Increased MD in CC and CST, as well as decreased AAC in CG, was correlated with a diagnosis of PSP compared to IPD.ConclusionsDTT can be used for demonstrating disease-specific regional white matter changes in parkinsonian disorders. The anterior portion of the CC was identified as a promising region for detection of neurodegenerative changes in patients with PSP, as well as for differential diagnosis between PSP and IPD.

Diffusion kurtosis imaging (DKI) is an emerging technique with the potential to quantify properties of tissue microstructure that may not be observable using diffusion tensor imaging (DTI). In order to help design DKI studies and improve interpretation of DKI results, we employed statistical power analysis to characterize three aspects of variability in four DKI parameters; the mean diffusivity, fractional anisotropy, mean kurtosis, and radial kurtosis. First, we quantified the variability in terms of the group size required to obtain a statistical power of 0.9. Second, we investigated the relative contribution of imaging and post-processing noise to the total variance, in order to estimate the benefits of longer scan times versus the inclusion of more subjects. Third, we evaluated the potential benefit of including additional covariates such as the size of the structure when testing for differences in group means. The analysis was performed in three major white matter structures of the brain: the superior cingulum, the corticospinal tract, and the mid-sagittal corpus callosum, extracted using diffusion tensor tractography and DKI data acquired in a healthy cohort. The results showed heterogeneous variability across and within the white matter structures. Thus, the statistical power varies depending on parameter and location, which is important to consider if a pathogenesis pattern is inferred from DKI data. In the data presented, inter-subject differences contributed more than imaging noise to the total variability, making it more efficient to include more subjects rather than extending the scan-time per subject. Finally, strong correlations between DKI parameters and the structure size were found for the cingulum and corpus callosum. Structure size should thus be considered when quantifying DKI parameters, either to control for its potentially confounding effect, or as a means of reducing unexplained variance.

Biophysical models that describe the outcome of white matter diffusion MRI experiments have various degrees of complexity. While the simplest models assume equal-sized and parallel axons, more elaborate ones may include distributions of axon diameters and axonal orientation dispersions. These microstructural features can be inferred from diffusion-weighted signal attenuation curves by solving an inverse problem, validated in several Monte Carlo simulation studies. Model development has been paralleled by microscopy studies of the microstructure of excised and fixed nerves, confirming that axon diameter estimates from diffusion measurements agree with those from microscopy. However, results obtained in vivo are less conclusive. For example, the amount of slowly diffusing water is lower than expected, and the diffusion-encoded signal is apparently insensitive to diffusion time variations, contrary to what may be expected. Recent understandings of the resolution limit in diffusion MRI, the rate of water exchange, and the presence of microscopic axonal undulation and axonal orientation dispersions may, however, explain such apparent contradictions. Knowledge of the effects of biophysical mechanisms on water diffusion in tissue can be used to predict the outcome of diffusion tensor imaging (DTI) and of diffusion kurtosis imaging (DKI) studies. Alterations of DTI or DKI parameters found in studies of pathologies such as ischemic stroke can thus be compared with those predicted by modelling. Observations in agreement with the predictions strengthen the credibility of biophysical models; those in disagreement could provide clues of how to improve them. DKI is particularly suited for this purpose; it is performed using higher b-values than DTI, and thus carries more information about the tissue microstructure. The purpose of this review is to provide an update on the current understanding of how various properties of the tissue microstructure and the rate of water exchange between microenvironments are reflected in diffusion MRI measurements. We focus on the use of biophysical models for extracting tissue-specific parameters from data obtained with single PGSE sequences on clinical MRI scanners, but results obtained with animal MRI scanners are also considered. While modelling of white matter is the central theme, experiments on model systems that highlight important aspects of the biophysical models are also reviewed.

BACKGROUND: 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. (Less)

Background The clinical presentation in progressive supranuclear palsy (PSP), an atypical parkinsonian disorder, includes varying degrees of frontal dysexecutive symptoms. Using diffusion tensor imaging (DTI) and tractography (DTT), we investigated whether diffusion changes and atrophy of the inferior fronto-occipital fasciculus (IFO) occurs in PSP and if these changes correlate with disease stage and clinical phenotype. The corticospinal tract (CST), which is often involved in PSP, was investigated for comparison. Methods DTI of the whole brain was performed with a 3 T MR scanner using a single shot-EPI sequence with diffusion encoding in 48 directions. Scans were obtained in patients with PSP (n = 13) and healthy age-matched controls (n = 12). DTT of the IFO and CST was performed with the PRIDE fibre tracking tool (Philips Medical System). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were calculated and correlated with disease stage and clinical phenotype. Results In patients with PSP, significantly decreased FA and increased ADC was found in the frontal part of IFO compared with the medial and occipital parts of IFO, as well as compared to controls. Four of the thirteen patients with PSP showed a marked decrease in the number of tracked voxels in the frontal part of IFO. These findings were most pronounced in patients with severe frontal cognitive symptoms, such as dysexecutive problems, apathy and personality change. There was a strong correlation (r2 = -0.84; p < 0,001) between disease stage and FA and ADC values in the CST. Conclusions DTT for identification of neuronal tracts with subsequent measurement of FA and ADC is a useful diagnostic tool for demonstrating patterns of neuronal tract involvement in neurodegenerative disease. In selected tracts, FA and ADC values might act as surrogate markers for disease stage.

Two relatives, a 61-year-old man and the 21-year-old grandson of his sister, suffered from bilateral visual loss and were diagnosed with Leber hereditary optic neuropathy. In both cases, the diagnosis was molecularly confirmed with the 11778 mitochondrial mutation. MRI showed increased T2 signal not only in the optic nerves and chiasm but also in the optic tracts, extending to the lateral geniculate bodies. To our knowledge, the latter finding has not been described previously.

Many axons follow wave-like undulating courses. This is a general feature of extracranial nerve segments, but is also found in some intracranial nervous tissue. The importance of axonal undulation has previously been considered, for example, in the context of biomechanics, where it has been shown that posture affects undulation properties. However, the importance of axonal undulation in the context of diffusion MR measurements has not been investigated. Using an analytical model and Monte Carlo simulations of water diffusion, this study compared undulating and straight axons in terms of diffusion propagators, diffusion-weighted signal intensities and parameters derived from diffusion tensor imaging, such as the mean diffusivity (MD), the eigenvalues and the fractional anisotropy (FA). All parameters were strongly affected by the presence of undulation. The diffusivity perpendicular to the undulating axons increased with the undulation amplitude, thus resembling that of straight axons with larger diameters. Consequently, models assuming straight axons for the estimation of the axon diameter from diffusion MR measurements might overestimate the diameter if undulation is present. FA decreased from approximately 0.7 to 0.5 when axonal undulation was introduced into the simulation model structure. Our results indicate that axonal undulation may play a role in diffusion measurements when investigating, for example, the optic and sciatic nerves and the spinal cord. The simulations also demonstrate that the stretching or compression of neuronal tissue comprising undulating axons alters the observed water diffusivity, suggesting that posture may be of importance for the outcome of diffusion MRI measurements.

In a 16-year-old boy with hemiplegia and severe, intractable epilepsy after a neonatal cerebral ischemic insult, cortical motor control was only equivocally assessed by functional magnetic resonance imaging. Therefore, high-precision navigated transcranial magnetic stimulation was performed, which demonstrated that cortical control of muscles on the paretic side was selectively affected. Leg muscle control was located in the contralateral hemisphere, as expected in healthy individuals, whereas forearm muscles were controlled from both hemispheres, and hand muscles were controlled only from the hemisphere ipsilateral to the paresis.

A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected, but was not associated with disease state.

The aims of the studies were: to evaluate the spatial resolution of fMRI at 3 T by studying fingersomatotopy in area 3 b of the primary sensory area (Paper 1); to investigate the potential of fMRI at 3T as a clinical tool for preoperative evaluation of patients with intracranial tumors (Paper 2); to investigate the effect of glioma resection on the spatial extent of fMRI activation as compared to the normal within-subject variability (Paper 3); to determine whether the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) can distinguish tumor-infiltrated edema of gliomas from pure edema of meningiomas and metastases (Paper 4). Results: Strict somatotopic organisation in the primary sensory cortex was shown in the group average; at the subject level the thumb was located laterally, anteriorly and inferiorly to the little finger in 94 % of subjects (Paper 1). The sensorimotor and language areas close to intracranial tumors were identified in 95 % of patients. Paradigm effectiveness ranged from 79 to 95 %. The median quality of the activation maps was high. fMRI contributed to the decision to operate, the surgical approach and the extent of the resection in 9, 13 and 12 patients, respectively (Paper 2). BOLD activation obtained from fMRI with motor, sensory and language stimulation pre- and postoperatively in glioma patients yielded differences in the spatial extent similar to those obtained from repeated examinations in healthy controls (Paper 3). Values and lesion-to-brain ratios of ADC and FA in peritumoral edema did not differ between high grade gliomas, meningiomas and metastases (Paper 4). Conclusions: Our results suggest that the spatial resolution of fMRI using a clinical protocol is adequate for localisation of the sensory representation of a finger (Paper 1). Preoperative fMRI for mapping of motor, sensory and language functions at 3 T is feasible and contributes to neurosurgical decision making (Paper 2). Longitudinal pre- and postoperative fMRI studies may be performed in patients with gliomas without concerns for potential effects of the decreased tumor volume on the BOLD effect as a possible source of error (Paper 3). Values and lesion-to-brain ratios of ADC and FA may not be useful to distinguish pure edema from tumor-infiltrated edema in peritumoral areas with T2-signal changes (Paper 4). Hjärntumörer är relativt vanligt förekommande och antalet nydiagnostiserade fall per år är i ökande. Vid utredning och uppföljning av patienter med misstänkt eller fastställd hjärntumör spelar bildgivande tekniker en betydande roll, med som förstahands metod magnetisk resonanstomografi (MR). Under det senaste decenniet har MR utvecklats från att framställa bilder på hjärnan till att inkludera mätning av fysiologiska variabler, som hjärnans blodflöde (perfusion), vattenmolekylernas rörelse (diffusion) inklusive avbildning av nervbanorna(Diffusion Tensor Imaging, DTI), bestämning av hjärnans kemiska sammansättning (MR spektroskopi, MRS) och mätning av nervcellsaktivitet (funktionell MR, fMRI). Teknikerna är tillgängliga för kliniskt bruk och har fått ytterligare intresse och spridning med introduktionen av MR-kameror med den högre fältstyrka 3 Tesla (T), att jämföra med tidigare gängse 1.5 T. I samband med installationen av 3 T MR-kamera på Neuroröntgen i Lund i januari 2002, kunde fMRI utföras i större utsträckning och med modern teknik. Då initierades detta avhandlingsarbete. I avhandlingen undersöks värdet av två av dessa tekniker, fMRI och DTI, vid utredningen av hjärntumörer. fMRI mäter ändringar i syresättningen i små blodkärl när nervcellerna aktiveras, exempelvis när handens känselbark stimuleras genom att rytmiskt stryka över handen med ett strävt föremål. Resultatet är en så kallad aktiveringskarta av hjärnan, där varje bildelement färgkodats beroende på dess aktivitetsgrad. Diffusion Tensor Imaging (DTI) är en typ av diffusions MR där vattenmolekylernas rörelse mäts i många riktningar. Metoden ger en uppfattning om huruvida denna rörelse föredrar något riktning i olika vävnader i hjärnan, till exempel sker den i den vita substansen företrädesvis utmed nervbanorna. I delarbete 1 undersöktes upplösningen vid fMRI genom att kartlägga fingrarnas representation i area 3 b i den sensoriska barken hos tjugo friska försökspersoner. En strikt ordning, såsom känd från tidigare undersökningar, återfanns på gruppnivå med tummen lokaliserad nedom, framför och vid sidan om lillfingret och däremellan de övriga fingrarna i vanlig ordning. På individnivå återfanns tummen nedom, framför och vid sidan om lillfingret hos 94 % av försökspersonerna och de övriga fingrarna mer utspridda däremellan. I delarbete 2 undersöktes tjugo patienter med intrakraniell tumör nära rörelse- och känselbarken eller språkfunktionen preoperativt med fMRI för att kartlägga dessa funktioners läge och bedöma avståndet till tumören. Den funktionen som låg närmast tumören enligt vad kunde förväntas från anatomin, identifierades hos 95 % av patienterna. Stimulering med hand- eller fotrörelse påvisade den motoriska barken hos 90 % av patienterna. Med borstning av hand eller fot påvisades känselbarken hos 95 %. Språkuppgifterna, bilda ord på viss bokstav och rimma, ak tiverade språkområdena i pann- och tinningloberna i mellan 79 % och 95 % av fallen. Aktiveringskartorna höll hög eller adekvat kvalitet hos 90 % av patienterna. fMRI var av värde för att bedöma huruvida patienten skulle opereras (9 patienter), för att planera operationen tekniskt (13) och för att bestämma operationens omfattning(12). I delarbete 3 undersöktes om variationerna i fMRI-aktiviteten efter operation för hjärntumör skiljer sig från variationen hos friska försökspersoner. Sex patienter med gliom undersöktes före operationen samt en vecka och två månader efter operationen; sex friska försökspersoner undersöktes tre upprepade gånger med jämförbart interval. Antalet bildelement som aktiverades vid stimulering av rörelse, känsel och språk i den respektive del av hjärnan bestämdes och låg till grunden för beräkning av ett så kallat lateralitetsindex (LI), där aktiveringen i höger och vänster hjärnhalva jämförs. Variationen hos patienterna skilde sig ej från den hos friska försökspersoner. I delarbete 4 undersöktes om två parametrar som kan beräknas från DTI-sekvenser, nämligen apparent diffusion coefficient (ADC) och fractional anisotropy (FA) är av värde för att skilja mellan tumörinfiltrerat ödem hos patienter med gliom och rent ödem hos patienter med meningeom och hjärnmetastaser. Trettio patienter (18 gliom, 7 meningeom och 5 metastaser) inkluderades. ADC och FA bestämdes (a) i området runt tumören med signalökning och (b) på motsvarande ställe i den andra hjärnhalvan. Kvoten mellan området runt tumören och dess motsvarighet i den andra hjärnhalvan beräknades. Någon skillnad i ADC eller FA mellan gliom, meningeom och metastaser framkom inte i varken värde eller kvot. Sammanfattningsvis talar våra resultat för att ett kliniskt fMRI-protokoll har tillräcklig hög upplösning för att identifiera enstaka fingrar. Preoperativ fMRI med kartläggning av rörelse, känsel och språkfunktionen kan utföras vid 3 T i klinsik miljö med gott resultat och är av värde för den neurokirurgiska bedömningen. Longitudinella fMRI-studier som inkluderar patienter pre- och postoperativt, kan utföras hos gliompatienter utan att resultaten drabbas av variationer i utbredningen av fMRI-aktiviteten. Värden och kvoter av ADC och FA är ej säkert av värde för att skilja mellan tumörinfiltrerat ödem och rent ödem.

Erratum Erratum to “Assessment of spatial BOLD sensitivity variations in fMRI using gradient-echo field maps” [Magn Reson Imaging 28 (2010) 947–956] Peter Mannfolk⁎, Ronnie Wirestam, Markus Nilsson, Danielle van Westen, Freddy Stahlberg , Johan Olsrud Department of Medical Radiation Physics, Clinical Sciences Lund, Lund University, Barngatan 2B, SE-22185 Lund, Sweden Department of Diagnostic Radiology, Clinical Sciences Lund, Lund University, SE-22185 Lund, Sweden Centre for Medical Imaging and Physiology, Skane University Hospital, Lund, MR Department, SE-22185 Lund, Sweden

Background: The primary sensory cortex (S1) in the postcentral gyrus is comprised of four areas that each contain a body map, where the representation of the hand is located with the thumb most laterally, anteriorly and inferiorly and the little finger most medially, posteriorly and superiorly. Previous studies on somatotopy using functional MRI have either used low field strength, have included a small number of subjects or failed to attribute activations to any area within S1. In the present study we included twenty subjects, who were investigated at 3 Tesla (T). We focused specifically on Brodmann area 3b, which neurons have discrete receptive fields with a potentially more clearcut somatotopic organisation. The spatial distribution for all fingers' peak activation was determined and group as well as individual analysis was performed. Results: Activation maps from 18 subjects were of adequate quality; in 17 subjects activations were present for all fingers and these data were further analysed. In the group analysis the thumb was located most laterally, anteriorly and inferiorly with the other fingers sequentially positioned more medially, posteriorly and superiorly. At the individual level this somatotopic relationship was present for the thumb and little finger, with a higher variability for the fingers in between. The Euclidian distance between the first and fifth finger was 17.2 mm, between the first and second finger 10.6 mm and between the remaining fingers on average 6.3 mm. Conclusion: Results from the group analysis, that is both the location of the fingers and the Euclidian distances, are well comparable to results from previous studies using a wide range of modalities. On the subject level the spatial localisation of the fingers showed a less stringent somatotopic order so that the location of a finger in a single subject cannot be predicted from the group result.

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.In the present series 1010 patients with unclear groin pain underwent herniography.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.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.

Markers for measuring the glomerular filtration rate (GFR) are filtered from plasma through the glomeruli and should have minimal excretion or reabsorption through the renal tubules and minimal extrarenal excretion. There is an increasing use of urographic contrast media as GFR markers (1). Examples are diatrizoate or iothalamate labeled with 125I or 131I, and nonradioactive nonionic media (such as iohexol and others). GFR is measured in milliliters per minute and is the virtual plasma volume (milliliters) from which the kidneys in 1 minute completely clear (remove) a GFR marker. In the following text, the term clearance refers to “clearance from the plasma compartment.” GFR was originally measured with renal clearance technique, which required a catheter in the bladder for collection of marker in the urine in addition to measurement of the concentration of marker in the plasma. This renal clearance technique measures the clearance of a GFR marker from plasma by the kidneys alone but involves a risk of infection from the catheter in the bladder or an inaccurate urine sampling as a source of error when no catheter is used. To avoid urine sampling, GFR is often measured as the body clearance of a GFR marker from plasma (ie, the total clearance of a marker from plasma by all of the organs of the body). This latter technique requires only plasma samples but has a source of error in that all GFR markers have some extrarenal excretion and an accompanying extrarenal clearance. The body clearance of a GFR marker will thus give a falsely high measurement of GFR because it gives the sum of “true GFR” and the extrarenal clearance of the marker. If the extrarenal clearances of GFR markers were known, or could be estimated, at different levels of GFR, this extrarenal clearance could be subtracted from the body clearance of the marker to get GFR values closer to the “true GFR.” With decreasing GFR, the extrarenal excretion and extrarenal clearance of a GFR marker could theoretically either increase to compensate for loss of renal function or remain stable or even decrease. In a number of investigations in humans and animals, the body clearances and the renal clearances of various GFR markers have been measured at different levels of GFR (2–10). The results are contradictory. In humans, the level of extrarenal clearance of GFR marker has been reported to be independent of decreasing GFR (9) and to decrease with decreasing GFR (10). In pigs with normal, reduced, or absent GFR, the total extrarenal clearances of iohexol and 51Cr-EDTA decreased with decreasing GFR and were lowest in the anuric pigs (P .01) (2,4–6). The total extrarenal excretion and the accompanying total extrarenal clearance of ionic and nonionic urographic contrast media include, inter alia, biliary and intestinal excretion and clearance (11–20). It may be expected that changes in the level of biliary clearance of the media are accompanied by similar changes in their total extrarenal clearance. Contrast medium filling of the gallbladder and biliary tract is sometimes observed on plain radiographs or computed tomographic (CT) examinations of the abdomen after injection of urographic contrast media. The phenomenon seems to increase in frequency with increasing dose of contrast medium and/or decreasing GFR. We Acad Radiol 2002; 9(suppl 1):S58–S61