Anatomical subgroup analysis of the MERIDIAN cohort: failed commissuration.

OBJECTIVE: To assess the contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with either agenesis or hypogenesis of the corpus callosum (referred to collectively as failed commissuration) on antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study of fetuses with failed commissuration (with or without ventriculomegaly) diagnosed on ultrasound in women who had MRI assessment within 2 weeks of ultrasound and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI was studied, as well as indicators of diagnostic confidence and effects on prognosis/clinical management. Appropriate diagnostic confidence was assessed by the score-based weighted average method, which combines diagnostic accuracy with diagnostic confidence data. RESULTS: In the MERIDIAN cohort, 79 fetuses were diagnosed with failed commissuration on ultrasound (55 with agenesis and 24 with hypogenesis of the corpus callosum). The diagnostic accuracy for detecting failed commissuration was 34.2% for ultrasound and 94.9% for MRI (difference, 60.7% (95% CI, 47.6-73.9%), P < 0.0001). The diagnostic accuracy for detecting hypogenesis of the corpus callosum as a discrete entity was 8.3% for ultrasound and 87.5% for MRI, and for detecting agenesis of the corpus callosum as a distinct entity was 40.0% for ultrasound and 92.7% for MRI. There was a statistically significant improvement in 'appropriate' diagnostic confidence when using MRI as assessed by the score-based weighted average method (P < 0.0001). Prognostic information given to the women changed in 36/79 (45.6%) cases after MRI and its overall effect on clinical management was 'significant', 'major' or 'decisive' in 35/79 cases (44.3%). CONCLUSIONS: Our data suggest that any woman whose fetus has failed commissuration as the only intracranial finding detected on ultrasound should have MRI examination for further evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Anatomical subgroup analysis of the MERIDIAN cohort: posterior fossa abnormalities.

OBJECTIVE: To assess the diagnostic and clinical contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with abnormalities of the posterior fossa as the only intracranial abnormality recognized on antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study of fetuses with abnormalities of the posterior fossa (with or without ventriculomegaly) diagnosed on antenatal ultrasound in women who had MRI within 2 weeks of ultrasound and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI is reported, as well as indicators of diagnostic confidence and effects on prognosis and clinical management. Appropriate diagnostic confidence was assessed by the score-based weighted average method, which combines diagnostic accuracy with diagnostic confidence data. RESULTS: Abnormalities confined to the posterior fossa according to ultrasound were found in 81 fetuses (67 with parenchymal and 14 with cerebrospinal fluid-containing lesions). The overall diagnostic accuracy for detecting an isolated posterior fossa abnormality was 65.4% for ultrasound and 87.7% for MRI (difference, 22.3% (95% CI, 14.0-30.5%); P < 0.0001). There was an improvement in 'appropriate' diagnostic confidence, as assessed by the score-based weighted average method (P < 0.0001), and a three-fold reduction in 'high confidence but incorrect diagnosis' was achieved using MRI. Prognostic information given to the women changed after MRI in 44% of cases, and the overall effect of MRI on clinical management was considered to be 'significant', 'major' or 'decisive' in 35% of cases. CONCLUSIONS: Our data suggest that any woman whose fetus has a posterior fossa abnormality as the only intracranial finding on ultrasound should have MRI for further evaluation. This is on the basis of improved diagnostic accuracy and confidence, which impacts substantially on the prognostic information given to women as well as their clinical management. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Anatomical subgroup analysis of the MERIDIAN cohort: ventriculomegaly.

OBJECTIVE: To assess the contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with ventriculomegaly (VM) as the only abnormal intracranial finding on antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study of fetuses with only VM diagnosed on ultrasound in women who had a subsequent MRI examination within 2 weeks and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI was reported in relation to the severity of VM. The difference in measurements of trigone size on the two imaging methods and the clinical impact of adding MRI to the diagnostic pathway were also studied. RESULTS: In 306 fetuses with VM, ultrasound failed to detect 31 additional brain abnormalities, having an overall diagnostic accuracy of 89.9% for ultrasound, whilst MRI correctly detected 27 of the additional brain abnormalities, having a diagnostic accuracy of 98.7% (P < 0.0001). There were other brain abnormalities in 14/244 fetuses with mild VM on ultrasound (diagnostic accuracy, 94.3%) and MRI correctly diagnosed 12 of these (diagnostic accuracy, 99.2%; P = 0.0005). There was a close agreement between the size of trigones measured on ultrasound and on MRI, with categorical differences in only 16% of cases, showing that MRI did not systematically overestimate or underestimate trigone size. Complete prognostic data were available in 295/306 fetuses and the prognosis category changed after MRI in 69/295 (23.4%) cases. The overall effect of MRI on clinical management was considered to be 'significant', 'major' or 'decisive' in 76/295 (25.8%) cases. CONCLUSION: Our data suggest that a woman carrying a fetus with VM as the only intracranial finding on ultrasound should be offered an adjuvant investigation by MRI for further evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

What neuroimaging should be performed in children in whom inflicted brain injury (iBI) is suspected? A systematic review.

AIMS: To investigate the optimal neuroradiological investigation strategy to identify inflicted brain injury (iBI). MATERIALS AND METHODS: A systematic review of studies published between 1970-2008 in any language was conducted, searching 20 databases and four websites, using over 100 keywords/phrases, supplemented by hand-searching of references. All studies underwent two independent reviews (with disagreements adjudicated by a third reviewer) by trained reviewers from paediatrics, paediatric neuroradiology and related disciplines, using standardized critical appraisal tools, and strict inclusion/exclusion criteria. We included primary studies that evaluated the diagnostic yield of magnetic resonance imaging (MRI), in addition to initial computed tomography (CT), or follow-up CT or ultrasound in children with suspected iBI. RESULTS: Of the 320 studies reviewed, 18 met the inclusion criteria, reflecting data on 367 children with iBI and 12 were published since 1998. When an MRI was conducted in addition to an abnormal early CT examination, additional information was found in 25% (95% CI: 18.3-33.16%) of children. The additional findings included further subdural haematoma, subarachnoid haemorrhage, shearing injury, ischaemia, and infarction; it also contributed to dating of injuries. Diffusion-weighted imaging (DWI) further enhanced the delineation of ischaemic changes, and assisted in prognosis. Repeat CT studies varied in timing and quality, and none were compared to the addition of an early MRI/DWI. CONCLUSIONS: In an acutely ill child, the optimal imaging strategy involves initial CT, followed by early MRI and DWI if early CT examination is abnormal, or there are ongoing clinical concerns. The role of repeat CT imaging, if early MRI is performed, is unclear, as is the place for MRI/DWI if initial CT examination is normal in an otherwise well child.

Cranial CT of the unconscious adult patient.

Unconscious patients are frequently referred to radiology departments for computed tomography (CT) of the brain. The objectives of these examinations are to define the underlying cause of impaired consciousness and in some cases to determine the severity of associated brain injury. There is often little history available to guide the clinician or radiologist, particularly in patients referred from the casualty department. In this review, we present the typical CT appearances of adult patients presenting with loss of consciousness for CT examination. We focus on the most common abnormalities that are identified in everyday radiological practice, emphasize important diagnostic signs that may enable a confident diagnosis to be made and discuss when further imaging may be warranted.

Indices of apoptosis and proliferation as potential prognostic markers in non-functioning pituitary adenomas.

OBJECTIVE: Non-functioning pituitary adenomas (NFAs) are a distinct group of pituitary adenomas, which comprise approximately 20% of pituitary adenomas. Although most pituitary adenomas are benign, there is a subset of adenomas that behaves in an aggressive fashion, with either invasion of the surrounding structures or recurrence. The aim of this study was to investigate whether the behaviour of NFAs can be predicted using immunohistochemical markers that label proliferating and apoptotic cells, including a new marker for apoptosis (M30 CytoDEATH). This is the first study to analyse both the proliferation labelling index (LI) and the apoptotic index (AI) in NFAs and to correlate the labelling indices of these histological markers with tumor growth rate as measured by 2 postoperative MRI scans. MATERIAL AND METHODS: 40 patients in total were included in the study. 20 patients with high growth rate and percentage change in the pituitary adenoma volume as assessed on 2 postoperative MRI scans were age/sex matched to 20 patients with low growth rate or percentage change. RESULTS: There is no significant statistical difference of the histological and immunohistochemical indices assessed between cases and controls. CONCLUSION: The routine assessment of the proliferation and the apoptotic markers used in this study in NFAs has no prognostic value.

T1 lesion load and cerebral atrophy as a marker for clinical progression in patients with multiple sclerosis. A prospective 18 months follow-up study.

We investigated the relationship between local tissue destruction, diffuse cerebral atrophy and clinical progression in patients with established multiple sclerosis (MS). Twenty-nine patients with MS (13 patients with relapsing--remitting and 16 with secondary progressive disease) were included in a prospective serial study. Cerebral volumes, T1 hypointense lesion volumes, T2 hyperintense lesion volumes at baseline and at 18 months follow-up, and the volume of monthly enhancing lesions from month 0 to month 9 were assessed on magnetic resonance imaging (MRI) brain scans using highly reproducible semi-automated quantitative techniques. The main outcome measures were the MRI parameters and disability on Kurtzkes' Expanded Disability Status Scale. There was a significant correlation between the change (increase) in T1 lesion volume and progressive cerebral atrophy, whereas no correlation between the T2 lesion volume and atrophy was seen over the same follow-up period. The change in T1 lesion volume correlated more strongly than did T2 lesion volume change with the change in disability. We conclude that hypointense abnormalities detected in T1-weighted brain scans and cerebral atrophy may be directly linked. Although one should bear in mind some potential for reversibility due to inflammatory, oedematous lesions, these MR measures are a useful marker of progressive tissue damage and clinical progression in established MS.

The effect of repositioning on brain MRI lesion load assessment in multiple sclerosis: reliability of subjective quality criteria.

The aim of this study was to assess the variability of lesion load measurements for repeated brain magnetic resonance imaging (MRI) scans judged to have either poor or good repositioning quality on the basis of subjective criteria used for clinical trials in multiple sclerosis (MS). Scan-rescan variability was also compared with the intra-observer variability assessed from three repeated volume measurements of the same scan. Nine patients with MS were studied; each of them underwent the scan-rescan procedure on the same day. Five scans were considered to have poor and four scans to have good repositioning. Between these two groups there were no differences in either the mean lesion loads or the measurement variance. For the whole group of patients, the intra-observer variability of repeated measurements gave a significantly lower coefficient of variation (COV = 4.9%) than the variability owing to repositioning (COV = 8.9%, P < 0.01, F test). Our results confirm that the effect of repositioning on brain MRI lesion load assessment is stronger than that owing to the intra-observer variability for repeated measurements and indicate that the simple visual judgment about the scan repositioning quality seems unable to predict the scan-rescan reproducibility.

MRI lesion volume measurement in multiple sclerosis and its correlation with disability: a comparison of fast fluid attenuated inversion recovery (fFLAIR) and spin echo sequences.

OBJECTIVES: To assess whether multiple sclerosis lesion volume measurements derived using the fast fluid attenuated inversion recovery (fFLAIR) sequence show better reproducibility or correlation with disability than those derived using the conventional spin echo (CSE) sequence. METHODS: Part I: twenty five patients with multiple sclerosis were scanned with CSE, fast spin echo (FSE), and fFLAIR. Lesion volume was determined twice for each sequence using a local threshold segmentation technique. Part II: fifty six patients with multiple sclerosis were scanned with CSE and fFLAIR. Total and regional brain lesion volumes were compared with the Kurtzke extended disability scale (EDSS) and functional systems scores (FSS). RESULTS: Part I: analysis times were significantly longer for CSE than for FSE or fFLAIR. There was no significant difference in the reproducibility of the three sequences. Part II: total lesion volumes were similar but posterior fossa lesion volumes were significantly greater for CSE and subcortical lesion volumes significantly greater for fFLAIR. There was a significant correlation between total volume and EDSS with both sequences (CSE r=0.49; fFLAIR r=0.44). Correlations for the two sequences showed minor differences when anatomical region and FSS were considered separately. CONCLUSIONS: CSE, FSE, and fFLAIR are equally reproducible; FSE yields lower volumes than CSE; fFLAIR gives similar volumes to CSE but underscores the posterior fossa. Overall clinical correlations are similar for CSE and fFLAIR.

Effect of training and different measurement strategies on the reproducibility of brain MRI lesion load measurements in multiple sclerosis.

In this study, we evaluated the intra- and interobserver variabilities in measuring lesion load of brain MRI abnormalities present on proton-density scans from patients with MS, using using both manual outlining or a semiautomated local thresholding technique (LTT). We also evaluated how these variabilities were affected by the use of standard rules for lesion load measurements, training, and different measurement strategies. The intraobserver variabilities obtained after establishing rules for lesion load measurements and training were not significantly different from those obtained before any consensus among the observers, both for manual outlining and for the LTT. On the contrary, the interobserver variabilities obtained with manual outlining or the LTT were significantly reduced when rules for lesion load measurements were used. For manual outlining, the intraobserver variability did not significantly change when the measurements were performed after an experienced radiologist identified lesions or when using adjacent slices and the corresponding T2-weighted images as reference for lesion identification. On the contrary, for the LTT, the intraobserver variability was significantly reduced by the use of the radiologic marking. The interobserver variabilities for both manual outlining and the LTT were reduced compared with the free condition when these measurement strategies were used. Our findings demonstrate that both lesion identification and outlining are important sources of variation for MRI lesion load measurements in MS and that there are simple strategies to reduce such variation that might be useful when planning clinical trials.

Multiple sclerosis lesion detection in the brain: a comparison of fast fluid-attenuated inversion recovery and conventional T2-weighted dual spin echo.

We performed fast fluid-attenuated inversion recovery (fFLAIR) and conventional spin echo (CSE) brain MRI in 32 multiple sclerosis (MS) patients (eight each benign, relapsing-remitting, primary progressive, and secondary progressive). We compared number and site of lesions detected on each sequence. With initial separate assessment, we identified a total of 3,668 lesions-2,892 by CSE and 2,943 by fFLAIR. Following simultaneous review of the sequences, we identified an additional 217 lesions on fFLAIR and 229 on CSE. fFLAIR detected fewer lesions in the posterior fossa (66 versus 138, p = 0.001), fewer small (< 5 mm) discrete cerebral white matter lesions (671 versus 829, p = 0.0002), more subcortical lesions (542 versus 306, p < 0.0001), and more large discrete lesions (419 versus 385, p = 0.0006). Its relatively poor detection of posterior fossa lesions makes it premature for fFLAIR to replace CSE as the primary sequence for detecting MS lesions in clinical trials.

Interscanner variation in brain MRI lesion load measurements in MS: implications for clinical trials.

We evaluated the effect of interscanner variation on brain MRI-measured lesion volumes and measurement reproducibility in MS. Twenty clinically definite MS patients were each scanned on two or three scanners (a total of 14 scanners were used). In addition, a formalin-fixed MS brain was studied on eight scanners from different manufacturers and with different field strengths. For the formalin-fixed MS brain, on each machine we obtained two scans with slice thicknesses of 5 and 3 mm. Only 5-mm-thick slices were obtained from patients. The lesion volume present on each scan was evaluated three times by a single observer in random order, using a local thresholding technique. In two groups of eight patients scanned on machines with different field strengths, the mean lesion volumes present on scans obtained at 1.5 T were significantly higher than those measured on scans obtained with machines operating at 0.5 and 1.0 T (p < 0.01). When a single observer repeatedly evaluated the same scan, a median introbserver agreement of 98.7% (95% CI, 97.9 to 99.1) was achieved. However, when the observer evaluated the scans from different MRI scanners, the agreement (an interscanner agreement) fell to 91.1% (CI, 90.2 to 94.1). When only scanners operating at 1.5 T were considered, the median interscanner agreement was 96.7% (CI, 95 to 97.5). Also, for the formalin-fixed MS brain, the intraobserver agreements obtained with both slice thicknesses were significantly higher than the corresponding interscanner agreements. The interscanner agreement, but not the intraobserver agreement, obtained with a slice thickness of 3 mm was higher than that obtained with a slice thickness of 5 mm. Our results indicate that lesion volume measurements in MS are influenced significantly by the use of different MR scanners and that a patient included in a serial study should be always scanned with the same MR machine using 3-mm thick slices.

Magnetisation transfer ratio measurement in the cervical spinal cord: a preliminary study in multiple sclerosis.

MRI readily detects the lesions of multiple sclerosis (MS) in the brain and spinal cord. Conventional MRI sequences do not, however, permit distinction between the various pathological characteristics (oedema, demyelination, axonal loss and gliosis) of lesions in MS. Magnetisation transfer (MT) imaging may be more specific in distinguishing the pathologies responsible for disability in MS, namely demyelination and axonal loss, and therefore may have a potential role in monitoring treatment. We have applied MT imaging to the cervical spinal cord to see if it is feasible to measure MT ratios (MTR) in this region where pathological changes may result in considerable disability. We studied 12 patients with MS and 12 age- and sex-matched normal controls using a sagittal T2-weighted fast spin-echo sequence with and without an MT pulse. The median value for cervical cord mean MTR measurement in normal controls was 19.30% units (interquartile range 19.05-19.55), whereas values were significantly lower in MS patients (median = 17.95% units, interquartile range 17.25-19.00, P = 0.0004). There was a low intrarater variability for repeated mean MTR measurements. We conclude that it is possible to measure MTR in the cervical spinal cord, that a significant reduction occurs in patients with MS, and that there may be a role for this measure in future MS treatment trials.

Fast FLAIR of the brain: the range of appearances in normal subjects and its application to quantification of white-matter disease.

Axial fast FLAIR images of the brains of 40 normal volunteers in four age groups between 16 and 55 years were examined and the number and size of areas of increased white-matter signal recorded. Increased signal in the corticospinal tract region was seen at the level of the internal capsule in all subjects, extending up towards the centrum semiovale and down towards the pons for 0.5-5.5 cm (median 2.5 cm). In all cases the IIIrd and IVth ventricles were outlined by a thin line of high signal. Focal areas of high signal (caps) were seen around the frontal and occipital horns in 90% and 77% respectively; 54% of caps were asymmetrical. None of the above features varied with the age or sex of the subject, but the numbers of discrete white matter 'lesions' increased with age. The findings are used to suggest guidelines for the identification of areas of 'normal' high signal to be excluded in quantification of lesions on fast FLAIR images.

A comparison of conventional and fast spin-echo sequences for the measurement of lesion load in multiple sclerosis using a semi-automated contour technique.

Changes on serial assessments of brain MRI lesion load are used for monitoring therapeutic efficacy in patients with multiple sclerosis (MS). We assessed the accuracy and reliability of conventional spin-echo (CSE) and fast spin-echo (FSE) sequences for measurement of lesion volume using a semiautomated contour technique. Cranial CSE and FSE examinations of 18 patients with secondary progressive MS were studied. The mean lesion load was slightly higher with the CSE sequence (p = 0.002). Intraobserver variability was significantly higher for FSE than for CSE, according to both the coefficient of variation between two measurements (mean 2.48% and 1.35% respectively, p < 0.05) and back-transformed 95% limits of agreement (1.005-1.060 for FSE; 0.988-1.019 for CSE). Although FSE sequences are quicker and the total lesion volume measurements are similar to those obtained with CSE, the poorer reproducibility raises doubts about the use of FSE to replace CSE in clinical trials.

Imaging of the spinal cord and brain in multiple sclerosis: a comparative study between fast FLAIR and fast spin echo.

Recent reports have suggested that fluid attenuated inversion recovery (FLAIR) is a technique superior to conventional (CSE) or fast spin echo (FSE) T2-weighted sequences in detecting intrinsic lesions both in the brain and spinal cord. We report our experience of an inversion recovery prepared FSE, which we refer to as fast FLAIR, in a comparative study of ten patients with clinically definite multiple sclerosis (MS) who underwent cervical cord and brain imaging with both FSE and fast FLAIR. The results showed that in the cerebral hemispheres fast FLAIR detected more lesions than FSE (P < 0.001). However, FSE detected more lesions than fast FLAIR in the posterior fossa (P = 0.02) and in the cord fast FLAIR was much inferior detecting only 2 of 33 lesions seen on FSE. Estimating the T2 relaxation times of lesions in each of three areas (periventricular, posterior fossa, cervical cord) showed that the T2 value of posterior fossa and cervical cord lesions was significantly lower than that of periventricular lesions, suggesting that the lesion composition is different and consequently their imaging appearances are different. In conclusion, although fast FLAIR improves the detection of MS lesions in the cerebral hemispheres, its substantially lower sensitivity in the posterior fossa and spinal cord is a potentially important limitation to its use as a tool for the diagnosis of MS and for monitoring therapies. Further studies are needed to elucidate the mechanisms underlying the loss of sensitivity.

Progressive cerebral atrophy in multiple sclerosis. A serial MRI study.

Recent studies of the spinal cord and cerebellum have highlighted the importance of atrophy in the development of neurological impairment in multiple sclerosis. We have therefore developed a technique to quantify the volume of another area commonly involved pathologically in multiple sclerosis: the cerebral white matter. The technique we describe extracts the brain from the skull on four contiguous 5 mm periventricular slices using an algorithm integrated in an image analysis package, and quantifies their volume. Intra-observer scan-rescan reproducibility was 0.56%. We have applied this technique serially to 29 patients with multiple sclerosis selected for an 18-month treatment trial with a monoclonal antibody against CD4+ lymphocytes (deemed clinically ineffective). A decrease in volume beyond the 95% confidence limits for measurement variation was seen in 16 patients by the end of the 18-month period. The rate of development of atrophy was significantly higher in those who had a sustained deterioration in their Kurtzke expanded disability status scale (EDSS) score compared with those who did not (respective means: -6.4 ml year-1 and -1.8 ml year-1, P < 0.05) but in both groups these changes differed significantly from baseline (P < 0.05). Baseline T2 lesion load, change in T2 lesion load over 18 months and the volume of new gadolinium enhancing lesions on monthly scans for the first 10 months showed no correlation with the development of atrophy. This study demonstrates that progressive cerebral atrophy can be detected in individual patients with multiple sclerosis, correlates with worsening disability and gives additional information to that obtained with conventional MRI. The effect of putative therapies aimed at preventing disability could be objectively assessed by this measure.

Lesion volume measurement in multiple sclerosis: how important is accurate repositioning?

This study was designed to estimate the contribution of repositioning inaccuracies to measured intracranial lesion volumes in multiple sclerosis (MS). Five patients with MS were each scanned 10 times, using spin-echo imaging (2,000/34/90), contiguous 5-mm slices, and different scanning positions. The maximum displacements from baseline were +/-4 degrees (AP rotation) and 3 mm (slice offset). Lesion volume was measured twice for each scan using a semiautomated contour technique. Measured lesion volumes ranged from 4,328 mm3 to 164,831 mm3. The mean intrarater coefficient of variation (CV) calculated for individual patients ranged from 1.1 to 4% (median, 1.7%). Using analysis of variance, the overall variance and CV due to altered scan position were greater than that due to rater error (repositioning CV 4.0%, intrarater CV 3.5%). The worst-case difference between volumes in the same patient ranged from 8.9 to 32% (median, 9.9%). Both rater and repositioning errors were greater for smaller lesion volumes. The maximum potential error due to repositioning inaccuracies is of a similar magnitude to the 5 to 10% expected change in lesion volume over 1 year. This study justifies continued careful attention to accuracy in repositioning for serial MR studies in patients with MS.