Neuroradiology diagnostic errors at a tertiary academic centre: effect of participation in tumour boards and physician experience.

AIM: To quantify and correlate the diagnostic error rates in radiological interpretation with the experience of the attending neuroradiologist at a tertiary academic medical centre. MATERIALS AND METHODS: The institution's Neuroradiology Quality Assurance Database of diagnostic errors was searched for misses from 2014-2020. Attendance at Head and Neck (H&N), Brain, and Paediatric Neuroradiology (PN) tumour boards (TB) as the presenting radiologist was recorded. Number of post-fellowship years of clinical practice (CPY) and frequency of TB attendance were considered separate metrics of a radiologist's experience. Radiological errors were categorised as Total, H&N, Skull Base (SKB), Brain, or PN diagnostic errors. Diagnostic error rates per attending neuroradiologist within each category were correlated with the frequency of TB participation and CPY using Spearman's rank correlation coefficients. RESULTS: A total 607 examinations contained a diagnostic error. Spearman's rank correlation coefficients between Total TB participation and Total, H&N, SKB, Brain error rates were: -0.89 (p=0.0002); -0.81 (p=0.002); -0.66 (p=0.03); -0.82 (p=0.002); respectively. Spearman's rank correlation coefficients between CPY and Total, H&N, SKB, Brain and PN error rates were: 0.05 (p=0.88); 0.08 (p=0.82); 0.28 (p=0.41); -0.10 (p=0.77); -0.16 (p=0.63), respectively. Spearman's rank correlation coefficients between H&N TB and H&N, SKB error rates; and between Brain TB attendance and Brain error rates were statistically significant (p<0.05). CONCLUSION: The present study shows a strong correlation between high TB participation rates and low diagnostic error rates. The number of years in practice did not appear to influence error rate.

Added value in stroke imaging: accuracy and utility of additional coronal diffusion-weighted imaging.

AIM: To evaluate the value of adding additional coronal diffusion-weighted imaging with the same section thickness as standard axial images to improve detection of small infarcts. MATERIALS AND METHODS: Axial and coronal diffusion-weighted images (4 or 5 mm section thickness, 1 mm gap) were studied retrospectively in two rounds of data collection. During the first round, two radiologists identified sub-centimetre infarcts on only axial images during one sitting, and only coronal images during a second sitting. During the second round, the two radiologists were asked to identify infarcts on only axial images during one sitting, and on both axial and coronal images simultaneously during the second sitting. An expert reviewer determined true infarcts and artefacts. Relative contrast-to-noise ratios (rCNR) and relative mean region of interest (rROI) within each lesion were calculated. RESULTS: During the first round, sensitivity for infarct detection for the two radiologists was 92.7% and 100% on axial and 95.1% and 92.7% on coronal, respectively. During the second round, sensitivity improved from 88.9% to 98.1% for both radiologists (p=0.03). Specificity improved but did not reach statistical significance (p=0.06 and 0.12). False-negative and false-positive lesions had lower rCNR and rROI values. CONCLUSION: Including both axial and coronal DWI images with the same section thickness in the stroke protocol improves detection of small infarcts, which can be misdiagnosed on a single imaging plane. A second imaging plane is particularly useful for subtle infarcts, even without acquiring thin-section images.

Analysis of misses in imaging of head and neck pathology by attending neuroradiologists at a single tertiary academic medical centre.

AIM: To analyse errors in head and neck (H&N) pathology made by attending neuroradiologists at a single tertiary-care centre. MATERIALS AND METHODS: A neuroradiology quality assurance (QA) database of radiological errors was searched for attending physician errors in H&N pathology from 2014-2020. Data were limited to computed tomography (CT) and magnetic resonance imaging (MRI) reports. Data were collected on missed pathologies and study types. Misses were grouped into three categories: central neck (thyroid gland, aerodigestive tract), lateral neck (salivary glands, lymph nodes, soft tissues), and face/orbits (orbits, sinuses, masticator space). RESULTS: During the study period, a total of 283,248 CT and MRI neuroradiology examinations were interpreted (all indications). Seventy-four H&N misses were identified comprising 85.1% perceptual and 14.9% interpretive errors. The distribution of errors was face/orbits (37.8%), central neck (36.5%), and lateral neck (25.7%). Clinically significant errors were found most commonly in the aerodigestive tract (21%), orbits (17.7%), masticator space, and parotid glands (14.5% each). The majority (67.6%) of the misses were detected on examinations that were not performed for a primary H&N indication; MRI brain was the most common examination (27%). Clearly malignant or potentially malignant masses accounted for 48.6% of all misses. CONCLUSION: The majority of H&N misses were perceptual and were detected on examinations not performed for a H&N indication. Clearly malignant or potentially malignant masses represented half of all misses.

Gadolinium Deposition within the Pediatric Brain: No Increased Intrinsic T1-Weighted Signal Intensity within the Dentate Nucleus following the Administration of a Minimum of 4 Doses of the Macrocyclic Agent Gadoteridol.

BACKGROUND AND PURPOSE: Our aim was to evaluate whether serial administration of the macrocyclic gadolinium-based contrast agent gadoteridol in children is associated with T1-weighted hyperintensity within the dentate nucleus, an imaging surrogate for gadolinium deposition. MATERIALS AND METHODS: We identified a retrospective cohort of 10 patients younger than 18 years of age who underwent between 4 and 8 gadoteridol-enhanced MR imaging examinations of the brain from 2016 to 2017. For comparison, we identified a retrospective cohort of 9 pediatric patients who each underwent 6 gadodiamide-enhanced MR imaging examinations. For each examination, both dentate nuclei were contoured on unenhanced images and the mean dentate-to-pons signal intensity ratio was calculated. Dentate-to-pons signal intensity ratios from the first and last scans were compared using paired t tests. RESULTS: In the gadoteridol group, there was no significant change in the mean dentate-to-pons signal intensity ratio from the first to the last scan (0.99 versus 0.99, P = .59). In the gadodiamide group, there was a significant increase in the mean dentate-to-pons signal intensity ratio from the first to the last scan (0.99 versus 1.10, P = .001). CONCLUSIONS: Repeat administration of the macrocyclic gadolinium-based contrast agent gadoteridol in children was not associated with T1-weighted dentate hyperintensity, while the repeat administration of the linear gadolinium-based contrast agent gadodiamide was associated with T1-weighted dentate hyperintensity, presumably due to gadolinium deposition.

Relationships between regional neuronal loss and neurofibrillary changes in the hippocampal formation and duration and severity of Alzheimer disease.

The total numbers of neurons with and without neurofibrillary changes in the hippocampal subdivisions were estimated in 16 subjects with Alzheimer disease (AD) and in 5 normal elderly controls. On the basis of clinical symptoms, AD patients were subdivided into relatively less (AD-1. Functional Assessment Staging [FAST] stages 7a to 7c) and more severely affected (AD-2, FAST stages 7e to 7f) patient groups. In the AD-1 group relative to controls, the total number of neurons was reduced only in CA1 and in the subiculum. In the AD-2 group, neuronal losses were found in all sectors of the cornu Ammonis and in the subiculum and ranged from 53% in CA3 to 86% in CA1. The dentate gyrus was the only hippocampal subdivision without significant neuronal loss. Within the combined AD patient groups, significant correlations were noted between both clinical stage and duration of AD and both the total number of neurons and the percentage of neurons with neurofibrillary changes in CA1, CA4, and the subiculum. Regression analyses predicted neuronal losses over the maximal observed duration of 22 years of 87% in CA1, 63% in CA4, and 77% in the subiculum. Our data suggest that over the course of AD, continuous neurofibrillary tangle formation and continuous neuronal loss occur in the hippocampal subdivisions. The rate of neuronal loss appears to be similar for CA1, CA4, and the subiculum.

Neurofibrillary pathology--correlation with hippocampal formation atrophy in Alzheimer disease.

The three-dimensionally reconstructed hippocampal formations in three patients with very severe, immobile Alzheimer disease (AD) and three age-matched nondemented individuals were examined for a correlation between atrophy of hippocampal formation subdivisions and neurofibrillary changes, neuronal loss, and extent of amyloid deposition in plaques and vessels. In AD, a similar severe volume loss was observed in both cellular layers and layers composed of fibers. A strong correlation between the decrease in the volume of hippocampal formation subdivisions and the decrease in the total number of neurons suggests a causative role for neuronal loss in hippocampal formation volumetric loss. Strong regional correlations between the relative decreases in the total number of neurons and the relative increases in the total number of neurofibrillary tangles implicates neurofibrillary pathology as a possible etiologic proximate factor in neuronal and volumetric loss in the hippocampal formation of AD patients.

Frequency of hippocampal formation atrophy in normal aging and Alzheimer's disease.

We used CT and MR to examine the frequency of occurrence of hippocampal formation atrophy (HA) in a research clinic population of 130 normal elderly, 72 nondemented patients with very mild memory and cognitive impairments (MCI), 73 mild Alzheimer's disease (AD) patients, and 130 patients with moderate to severe AD. HA was found in 29% of the normal elderly group and its frequency of occurrence was strongly related to increasing age. For normal elderly 60-75 years of age, 15% had HA: the proportion rose to 48% in subjects 76-90 years of age. Among the three groups of impaired patients, the frequencies of HA ranged from 78% in the MCI patients to 96% in the advanced AD group. Unlike the normal elderly group, the percentages were not related to age. In both the normal elderly group and MCI group disproportionately more males than females had HA. After controlling for learning and the effects of generalized brain changes as reflected in ventricular size, only in the normal group was HA associated with reduced delayed verbal recall performance. Follow-up examinations for 15 individuals with baseline HA. 4 who at entry were MCI and 11 probable AD, yielded clinical and neuropathologic diagnoses of AD in all cases. The results of the present study indicate that hippocampal formation atrophy is associated with memory and cognitive impairments. Further longitudinal and neuropathologic work is required to validate the relationship between hippocampal formation atrophy and AD.

The histological validation of post mortem magnetic resonance imaging-determined hippocampal volume in Alzheimer's disease.

For 11 AD cases and four normal elderly controls, post mortem volumes of the hippocampal subdivisions were calculated by using magnetic resonance imaging and histological sections. After at least six weeks of fixation in formalin, brains were examined on a 1.5-T Philips Gyroscan imager producing T1-weighted coronal images with a 3-mm slice thickness. Brains were then processed and embedded in paraffin. Serial coronal sections, 3 mm apart and stained with Cresyl Violet, were used for the planimetry and unbiased estimation of the total numbers of neurons in the hippocampal subdivisions. For all 15 cases, magnetic resonance imaging- and histology-based measurements were performed along the whole rostrocaudal extent of the hippocampal formation and included three subvolumes: (i) the hippocampus (CA1-CA4 and the dentate gyrus); (ii) hippocampus/subiculum; and (iii) hippocampus/parahippocampal gyrus. After controlling for shrinkage, strong correlations were found between magnetic resonance imaging and histological measurements for the hippocampus (r = 0.97, P < 0.001), hippocampus/subiculum (r = 0.95, P < 0.001) and hippocampus/parahippocampal gyrus (r = 0.89, P < 0.001). We also calculated the total number of neurons in the hippocampus and hippocampus/subiculum subvolumes. Strong correlations between the magnetic resonance imaging subvolumes and neuronal counts were found for the hippocampus (r = 0.90, P < 0.001) and the hippocampus/subiculum subvolume (r = 0.84, P < 0.001). We conclude that very accurate volumetric measurements of the whole hippocampal formation can be obtained by using a magnetic resonance imaging protocol. Moreover, the strong correlations between magnetic resonance imaging-based hippocampal volumes and neuronal numbers suggest the anatomical validity of magnetic resonance imaging volume measurements.

In vivo structural studies of the hippocampus in normal aging and in incipient Alzheimer's disease.

Population trends indicate that in the near future the size of the elderly population will increase. This will result in a large increment in the numbers of persons suffering mild to severe levels of cognitive impairment. While considerable efforts continue to be made to explain brain changes associated with Alzheimer disease (AD), little is known of the brain changes in aging without dementia or so-called normal aging. Pathologic studies suggest that the medial temporal lobe is informative in the examination of the early brain changes related to AD. However, pathologic studies only offer a single observation and considerable uncertainty exists regarding the likelihood of progression of disease and the development of dementia. Several structural neuroimaging studies have recently investigated this anatomy and recent reports are encouraging for a medial temporal lobe based diagnosis for age-related cognitive impairments. We will present our findings on the MRI anatomy of the hippocampal formation as well as data bearing on the use of hippocampal formation imaging in the diagnosis of AD and as a predictive marker for future dementia. Our findings suggest an anatomically specific relationship between hippocampal volume and secondary memory performance. Because these observations apply to nondemented and normal elderly subjects, we are encouraged that the anatomy of age-related cognitive impairments can be reliably recognized and possibly put to use in therapeutic studies.

Duration of neurofibrillary changes in the hippocampal pyramidal neurons.

The total number of neurons with and without neurofibrillary changes in sectors CA1 to CA4, subiculum, and dentate gyrus of 16 subjects with Alzheimer disease (AD) was estimated. The duration of neurofibrillary changes was calculated on the basis of regressions between the duration of AD and neuronal numbers. In the CA1 and subiculum, it takes 3.4 and 5.4 years, respectively, for an intact neuron affected by neurofibrillary pathology to become a ghost tangle.

Neuronal and volume loss in CA1 of the hippocampal formation uniquely predicts duration and severity of Alzheimer disease.

In a series of multiple regression models predicting either duration or severity of Alzheimer disease (AD) patients, significant linear correlations were found consistently for the volume of CA1, the subiculum, and the entorhinal cortex. Similarly, the total number of neurons in CA1, CA4, and the subiculum was correlated significantly with both the duration and the severity of AD. A hierarchical multiple regression model was used to examine whether any of these intercorrelated measures had any unique relationship to disease duration or severity. The results showed that only CA1 demonstrated a unique contribution to the explained variance in predicting duration or severity of AD for volume and for neuronal numbers. These results indicate that in the hippocampal formation, volume and neuronal numbers of CA1 appear to show a unique relationship with clinical measures of AD.

MRI volume of the amygdala: a reliable method allowing separation from the hippocampal formation.

Studies of MRI-derived volume of the amygdala have been mostly performed on coronal sections where its boundaries with the hippocampus and the entorhinal cortex are indistinct. To date, all reports of in vivo amygdala volume have consistently overestimated the size of the structure. We have developed a method for the MRI-based in vivo measurement of the amygdala volume which allows a better separation of the amygdala from the adjoining hippocampal formation. In nine normal volunteers we obtained three-dimensional spoiled gradient recalled acquisition, 1.3-mm thick, T1 weighted sagittal MR images and created electronically linked reformatted images in the coronal and axial planes. On the original sagittal and the reformatted axial planes, where it is more readily apparent, we delineated the boundaries between the amygdala and the hippocampus and the amygdala and the hippocampo-amygdala transition area, respectively. We then projected those markings onto the coronal plane, where the other boundaries of the amygdala are more easily seen. Using these markings as a guide and utilizing extra-amygdalar coronal landmarks for the anterior end, we outlined the whole amygdala on the coronal plane and determined its volume. We observed that 45% of the coronal slices that contained amygdala also contained some hippocampus. The amygdala measurement had high test-retest reliability, with an intra-class correlation coefficient (rICC) of 0.99 for the total volume and an rICC of 0.93 for the measurement at the level of the individual slice. The average amygdala volume was 1.05 +/- 0.17 cm3 on the right and 1.14 +/- 0.15 cm3 on the left. Our amygdala volumes are in agreement with those reported in postmortem studies, which provides the reported method with face validity.

The insular claustrum in the methylazoxymethanol acetate (MAM) treated rats shows two different populations of neurons.

Methylazoxymethanol acetate (MAM) is a substance that inhibits migration of neurons in the embryonic brain. After intraperitoneal injection of two different doses of MAM to pregnant rats, microcephaly with or without complete development of the cerebral cortex was observed in every litter. High MAM doses (30 mg/kg) resulted in the lack of superficial layers (II-IV) of the cerebral cortex when the deep layers (V, VI) were seen. The claustrum was present but composed of loosely packed, medium-size, triangular or fusiform neurons with anarchic oriented long axes. After administration of low MAM doses (14 mg/kg) two different parts (medial and lateral) of the insular claustrum were observed. Our results suggest that neurons of the insular claustrum create two different subpopulations of cells, which were similar to that observed in primitive insectivore (e.g., hedgehog), but fuse in development.

The hippocampus in aging and Alzheimer's disease.

The role of imaging in the evaluation of neurodegenerative disorders is summarized. The primary role of imaging is to exclude potentially treatable disorders such as meningioma, extracerebral hematoma, Wernicke's disease, and hypothyroidism. Atrophic changes dominate in the hippocampal region on Alzheimer's disease versus the anterior, frontal, and temporal lobes in Pick's disease. Signal hypointensity in the putamen on T2-weighted spin-echo images favors poorly drug-responsive Parkinson's disease whereas putaminal hyperintensity is observed with Creutzfeldt-Jacob, Wilson's, and Leigh's diseases. As our population ages, a thorough understanding of imaging findings in a geriatric population assumes an increasing importance.

Nucleus limitans thalami--comparative anatomical study.

Cyto- and myeloarchitectonics as well as acetylcholinesterase activity of the nucleus limitans thalami--an important part of the nociceptive system--were studied in insectivora (Sorex araneus, Erinaceus europaeus, Talpa europaeus), rat, rabbit, cat, monkey and man. Our results suggest that nucleus limitans is phylogenetically a rather new structure. In insectivora and in the rat we could not find any evident group of neurons resembling nucleus limitans. In the rabbit and cat nucleus limitans is composed of few layers of elongated cells. In macaca and man it is a larger, more complicated structure possessing various types of neurons, and arranged into many layers.

Dilatation of the lateral part of the transverse fissure of the brain in Alzheimer's disease.

Post-mortem MRI (magnetic resonance images) studies followed by histopathological examination were used to study the size and the shape of the lateral part of the transverse fissure of the brain in seven individuals with Alzheimer disease (AD) and five controls. In control brains, the lateral part of the transverse fissure is a narrow cleft protruding laterally as choroid and hippocampal recesses. In AD-affected brains, the lateral part of the transverse fissure becomes a large subarachnoid space as a result of different degrees of atrophy of various hippocampal and parahippocampal structures. Our findings directly indicate the relationship between changes in the hippocampal and parahippocampal structures and the size of the lateral part of the transverse fissure. Sector CA1, the subiculum, the entorhinal cortex, and the parahippocampal isocortex are the most affected, whereas the dentate gyrus is much less affected. Adjacent thalamic structures, which are less vulnerable to the AD pathology, do not appear to contribute to transverse fissure changes. The size and the shape of the lateral part of the transverse fissure of the brain in AD reflect the atrophy of the hippocampus and parahippocampal structures.

The pathology of the claustrum in Galloway syndrome indicates the existence of claustro-entorhinal pathway.

The morphology of the claustrum in Galloway syndrome was investigated. Galloway syndrome is a rare autosomal recessive disease that causes microcephaly and is associated with kidney pathology. The brain examined was small, and the external surface of the hemispheres was lissencephalic, with an abnormal gyrification pattern. The whole cerebral cortex showed severe pathological changes, but the most affected area was the cortex lying on the medial aspect of the temporal lobe, especially the entorhinal cortex. In addition, the paraamygdalar and temporal parts of the claustrum were intensively changed. These results may confirm the opinion that the claustrum is a cortico-dependent structure and that the limbic cortex receives large projection from its ventral parts.

Overstaging of cartilage invasion by multidetector CT scan for laryngeal cancer and its potential effect on the use of organ preservation with chemoradiation.

OBJECTIVE: The two currently acceptable treatment options for locally advanced laryngeal cancer are total laryngectomy and organ preservation using chemoradiation. To facilitate therapeutic decision making, the accurate pre-treatment evaluation of cartilage invasion is of paramount importance. The purpose of this study was to evaluate the positive predictive value (PPV) and negative predictive value (NPV) of detecting neoplastic cartilage invasion in laryngeal cancer patients using fast-speed multidetector CT (MDCT). METHODS: 61 consecutive patients with clinically staged T3 or T4 squamous cell carcinoma of the larynx or hypopharynx who underwent total laryngectomy were analysed. All patients had MDCT of the neck within 2 weeks prior to surgery. Central radiographic and pathological review was performed in an attempt to correlate findings. MDCT invasion of cartilage was graded based on objective criteria. RESULTS: MDCT scan was found to have a PPV of 78% and an NPV of 100% for detection of invasion through cartilage, with sensitivity being 100% and specificity 96%. For detection of any cartilage invasion (minor, major or through cartilage invasion), PPV and NPV were 63% and 92%, respectively. The sensitivity was 85% and specificity was 75%. For the detection of tumour invasion through cartilage or major cartilage invasion, MDCT scan had a PPV of 53% and an NPV of 95%. 47% (9/19) patients were down-staged from T4 to T3 after central pathology review. CONCLUSION: The low PPV for cartilage destruction using MDCT suggests that a significant proportion of patients who were treated by total laryngectomy could have been appropriately offered organ preservation if more accurately staged at initial diagnosis.