Inter-modality assessment of medial temporal lobe atrophy in a non-demented population: application of a visual rating scale template across radiologists with varying clinical experience.

OBJECTIVES: To assess inter-modality agreement and accuracy for medial temporal lobe atrophy (MTA) ratings across radiologists with varying clinical experience in a non-demented population. METHODS: Four raters (two junior radiologists and two senior neuroradiologists) rated MTA on CT and MRI scans using Scheltens' MTA scale. Ratings were compared to a consensus rating by two experienced neuroradiologists for estimation of true positive and negative rates (TPR and TNR) and over- and underestimation of MTA. Inter-modality agreement expressed as Cohen's κ (dichotomized data), Cohen's κw, and two-way mixed, single measures, consistency ICC (ordinal data) were determined. Adequate agreement was defined as κ/κw ≥ 0.80 and ICC ≥ 0.80 (significance level at 95% CI ≥ 0.65). RESULTS: Forty-nine subjects (median age 72 years, 27% abnormal MTA) with cognitive impairment were included. Only junior radiologists achieved adequate agreement expressed as Cohen's κ. All raters achieved adequate agreement expressed as Cohen's κw and ICC. True positive rates varied from 69 to 100% and TNR varied from 85 to 100%. No under- or overestimation of MTA was observed. Ratings did not differ between radiologists. CONCLUSION: We conclude that radiologists with varying experience achieve adequate inter-modality agreement and similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. However, TPR varied between radiologists which could be attributed to rating style differences. KEY POINTS: • Radiologists with varying experience achieve adequate inter-modality agreement with similar accuracy when Scheltens' MTA scale is used to rate MTA on a non-demented population. • Differences in rating styles might affect accuracy, this was most evident for senior neuroradiologists, and only junior radiologists achieved adequate agreement on dichotomized (abnormal/normal) ratings. • The use of an MTA scale template might compensate for varying clinical experience which could make it applicable for clinical use.

Reporting frequency of radiology findings increases after introducing visual rating scales in the primary care diagnostic work up of subjective and mild cognitive impairment.

OBJECTIVES: Study the effect of introducing a template for radiological reporting of non-enhanced computed tomography (NECT) in the primary care diagnostic work up of cognitive impairment using visual rating scales (VRS). METHODS: Radiology reports were assessed regarding compliance with a contextual report template and the reporting of the parameters medial temporal lobe atrophy (MTA), white matter changes (WMC), global cortical atrophy (GCA), and width of lateral ventricles (WLV) using established VRS in two age-matched groups examined with NECT before (n = 111) and after (n = 125) the introduction of contextual reporting at our department. True positive rate (TPR) and true negative rate (TNR) before and after were compared. RESULTS: We observed a significant increase in the percentage of radiology reports with mentioning of MTA from 29 to 76% (p < 0.001), WMC from 69 to 86% (p < 0.01), and GCA from 54 to 82% (p < 0.001). We observed a significant increase in the percentages of reports where all of the parameters were mentioned, from 6 to 29% (p < 0.001). There was a significant increase in TPR from 10 to 55% for MTA. CONCLUSION: This study suggests that contextual radiological assessment using VRS could increase the reporting frequency of radiology findings in the diagnostic work up of cognitive impairment but compliance with templates may be difficult to endorse. KEY POINTS: • Introducing visual rating scales in clinical practice increases the reporting frequency of MTA, WMC, and GCA in the diagnostic work up of subjective and mild cognitive impairment. • Introducing visual rating scales has an effect on the true positive rate of reported MTA. • Compliance with contextual radiology templates remains low when use of the template is not enforced by the department leadership.

The potential role of T2*-weighted multi-echo data image combination as an imaging marker for intraplaque hemorrhage in carotid plaque imaging.

BACKGROUND: Carotid atherosclerotic plaques with intraplaque hemorrhage (IPH) are associated with elevated stroke risk. IPH is predominantly imaged based on paramagnetic properties of the upstream hemoglobin degradation product methemoglobin. This is an explorative observational study to test the feasibility of a spoiled gradient echo based T2* weighted MRI sequence (3D MEDIC) for carotid plaque imaging, and to compare signs suggestive of the downstream degradation product hemosiderin on 3D MEDIC with signs of methemoglobin on a T1wBB sequence. METHODS: Patients with recent TIA or stroke were selected based on the presence on non-calcified plaque components on CTA to promote an enriched prevalence of IPH in the material. Patients (n = 42) underwent 3T MRI with 3D MEDIC and 2D turbo spin echo T1w black blood (T1wBB). Images were independently evaluated by two neuroradiologists and Cohens Kappa was used for inter-reader agreement for each sequence. RESULTS: The technical feasibility for 3D MEDIC, was 34/42 patients (81%). Non-calcified plaque components with susceptibility effect without simultaneous T1-shortening-a combination suggestive of hemosiderin, was seen in 13/34 of the plaques. An equally large group display elevated T1w signal in combination with signal loss on 3D MEDIC, a combination suggestive of both hemosiderin and methemoglobin. Cohen's kappa for inter-reader agreement was 0.64 (CI 0.345-0.925) for 3D MEDIC and 0.94 (CI 0.81-1.00) for T1wBB. CONCLUSIONS: 3D MEDIC shows signal loss, without elevated T1w signal on T1wBB, in non-calcified tissue in many plaques in this group of patients. If further studies, including histological verification, confirm that the 3D MEDIC susceptibility effect is indeed caused by hemosiderin, 3D MEDIC could aid in the detection of IPH, beyond elevation of T1w signal.

Structural imaging findings on non-enhanced computed tomography are severely underreported in the primary care diagnostic work-up of subjective cognitive decline.

PURPOSE: The purpose of this study was to investigate how structural imaging findings of medial temporal lobe atrophy (MTA), posterior cortical atrophy (PCA), global cortical atrophy (GCA), white matter changes (WMC), and Evans' index/width of lateral ventricles (EI/WLV) are reported in the primary care diagnostic work-up of patients with subjective cognitive decline or mild cognitive impairment. METHODS: We included 197 patients referred to a non-enhanced computed tomography (NECT) as part of the diagnostic work-up. We compared the frequencies of reported findings in radiology reports written by neuroradiologists and general radiologists with actual pathological findings in a second view done by a single neuroradiologist using the MTA, PCA, GCA, WMC, and EI/WLV visual rating scales. Structural findings were also compared to cognitive tests. RESULTS: We found that MTA and PCA were clearly underreported by both neuroradiologists and general radiologists. The presence of GCA and WMC was also underreported among general radiologists. Only MTA showed a clear association with cognitive test results. CONCLUSIONS: We believe that the use of visual rating scales should be put into clinical practice to increase the yield of clinical NECT exams in the investigation of cognitive impairment. Special emphasis should be put on reporting MTA.

MAP3K6 Mutations in a Neurovascular Disease Causing Stroke, Cognitive Impairment, and Tremor.

OBJECTIVE: To describe a possible novel genetic mechanism for cerebral small vessel disease (cSVD) and stroke. METHODS: We studied a Swedish kindred with ischemic stroke and intracerebral hemorrhage, tremor, dysautonomia, and mild cognitive decline. Members were examined clinically, radiologically, and by histopathology. Genetic workup included whole-exome sequencing (WES) and whole-genome sequencing (WGS) and intrafamilial cosegregation analyses. RESULTS: Fifteen family members were examined clinically. Twelve affected individuals had white matter hyperintensities and 1 or more of (1) stroke episodes, (2) clinically silent lacunar ischemic lesions, and (3) cognitive dysfunction. All affected individuals had tremor and/or atactic gait disturbance. Mild symmetric basal ganglia calcifications were seen in 3 affected members. Postmortem examination of 1 affected member showed pathologic alterations in both small and large arteries the brain. Skin biopsies of 3 affected members showed extracellular amorphous deposits within the subepidermal zone, which may represent degenerated arterioles. WES or WGS did not reveal any potentially disease-causing variants in known genes for cSVDs or idiopathic basal ganglia calcification, but identified 1 heterozygous variant, NM_004672.4 MAP3K6 c.322G>A p.(Asp108Asn), that cosegregated with the disease in this large family. MAP3K6 has known functions in angiogenesis and affects vascular endothelial growth factor expression, which may be implicated in cerebrovascular disease. CONCLUSIONS: Our data strongly suggest the MAP3K6 variant to be causative for this novel disease phenotype, but the absence of functional data and the present lack of additional families with this disease and MAP3K6 mutations still limit the formal evidence for the variant's pathogenicity.

Medial temporal atrophy in preclinical dementia: Visual and automated assessment during six year follow-up.

Medial temporal lobe (MTL) atrophy is an important morphological marker of many dementias and is closely related to cognitive decline. In this study we aimed to characterize longitudinal progression of MTL atrophy in 93 individuals with subjective cognitive decline and mild cognitive impairment followed up over six years, and to assess if clinical rating scales are able to detect these changes. All MRI images were visually rated according to Scheltens' scale of medial temporal atrophy (MTA) by two neuroradiologists and AVRA, a software for automated MTA ratings. The images were also segmented using FreeSurfer's longitudinal pipeline in order to compare the MTA ratings to volumes of the hippocampi and inferior lateral ventricles. We found that MTL atrophy rates increased with CSF biomarker abnormality, used to define preclinical stages of Alzheimer's Disease. Both AVRA's and the radiologists' MTA ratings showed similar longitudinal trends as the subcortical volumes, suggesting that visual rating scales provide a valid alternative to automatic segmentations. Our results further showed that it took more than 8 years on average for individuals with mild cognitive impairment, and an Alzheimer's disease biomarker profile, to increase the MTA score by one. This suggests that discrete MTA ratings are too coarse for tracking individual MTL atrophy in short time spans. While the MTA scores from each radiologist showed strong correlations to subcortical volumes, the inter-rater agreement was low. We conclude that the main limitation of quantifying MTL atrophy with visual ratings in clinics is the subjectiveness of the assessment.