Head-to-head comparison of [11C]methionine PET, [11C]choline PET, and 4-dimensional CT as second-line scans for detection of parathyroid adenomas in primary hyperparathyroidism.

PURPOSE: Accurate preoperative localization is imperative to guide surgery in primary hyperparathyroidism (pHPT). It remains unclear which second-line imaging technique is most effective after negative first-line imaging. In this study, we compare the diagnostic effectiveness of [11C]methionine PET/CT, [11C]choline PET/CT, and four dimensional (4D)-CT head-to-head in patients with pHPT, to explore which of these imaging techniques to use as a second-line scan. METHODS: We conducted a powered, prospective, blinded cohort study in patients with biochemically proven pHPT and prior negative or discordant first-line imaging consisting of ultrasonography and 99mTc-sestamibi. All patients underwent [11C]methionine PET/CT, [11C]choline PET/CT, and 4D-CT. At first, all scans were interpreted by a nuclear medicine physician, and a radiologist who were blinded from patient data and all imaging results. Next, a non-blinded scan reading was performed. The scan results were correlated with surgical and histopathological findings. Serum calcium values at least 6 months after surgery were used as gold standard for curation of HPT. RESULTS: A total of 32 patients were included in the study. With blinded evaluation, [11C]choline PET/CT was positive in 28 patients (88%), [11C]methionine PET/CT in 23 (72%), and 4D-CT in 15 patients (47%), respectively. In total, 30 patients have undergone surgery and 32 parathyroid lesions were histologically confirmed as parathyroid adenomas. Based on the blinded evaluation, lesion-based sensitivity of [11C]choline PET/CT, [11C]methionine PET/CT, and 4D-CT was respectively 85%, 67%, and 39%. The sensitivity of [11C]choline PET/CT differed significantly from that of [11C]methionine PET/CT and 4D-CT (p = 0.031 and p < 0.0005, respectively). CONCLUSION: In the setting of pHPT with negative first-line imaging, [11C]choline PET/CT is superior to [11C]methionine PET/CT and 4D-CT in localizing parathyroid adenomas, allowing correct localization in 85% of adenomas. Further studies are needed to determine cost-benefit and efficacy of these scans, including the timing of these scans as first- or second-line imaging techniques.

Prospective evaluation of multidimensional health-related quality of life after endoscopic endonasal surgery for pituitary adenomas using the endoscopic endonasal sinus and skull base surgery questionnaire.

Objective: Social functioning is an important factor in the evaluation of postoperative health-related quality of life (HRQoL) for pituitary adenoma patients. In a prospective cohort study multidimensional HRQoL of non-functioning (NFA) and functioning (FA) pituitary adenoma patients were evaluated following endoscopic endonasal surgery using the endoscopic endonasal sinus and skull base surgery questionnaire (EES-Q). Methods: Prospectively, 101 patients were included. The EES-Q was completed preoperatively and postoperatively (2 weeks, 3 months, 1 year). Sinonasal complaints were completed daily during the first week postoperatively. Preoperative and postoperative scores were compared. A generalized estimating equation (uni- and multivariate) analysis was performed to identify significant HRQoL changes related to selected covariates. Results: Two weeks postoperatively, physical (p < .05) and social (p < .05) HRQoL are worse and psychological (p < .05) HRQoL improved compared with preoperatively. Three months postoperatively, psychological HRQoL (p = .01) trended back to baseline and no differences in physical or social HRQoL were reported. One year postoperatively, psychological (p = .02) and social (p = .04) HRQoL improved while physical HRQoL remained stable. FA patients report a worse HRQoL preoperatively (social, p < .05) and 3 months postoperatively (social, p < .02 and psychological, p < .02). Sinonasal complaints peak in the first days postoperatively and gradually return to presurgical levels 3 months postoperatively. Conclusions: The EES-Q provides meaningful information on multidimensional HRQoL to improve patient-centred health care. Social functioning remains the most difficult area in which to achieve improvements. Despite the relatively modest sample size, there is some indication that the FA group continues to show a downward trend (and thus improvement) even after 3 months, when most other parameters reach stability. Level of evidence: Level II-B.

Radiologic Characteristics of Spinal Hemangioblastomas in von Hippel Lindau Disease as Guidance in Clinical Interventions.

OBJECTIVE: Hemangioblastomas in the central nervous system are the most common manifestation of von Hippel-Lindau (VHL) disease. Because the growth rate of hemangioblastomas is unpredictable, regular follow-up is mandatory, focusing on clinical symptoms and imaging of the central nervous system. However, clinical symptoms may be subtle and nonspecific, and data about the relationship between the radiologic findings and clinical symptoms are sparse. This study aims to evaluate if and how findings of magnetic resonance imaging (MRI) regarding spinal hemangioblastomas are associated with symptoms of VHL disease, with special attention to peritumoral edema and spinal cysts. METHODS: Serial spinal MRI scans of 43 genetically or clinically established VHL patients with at least 2 years of follow-up were reevaluated to examine the volume, growth rate, and location of spinal hemangioblastomas and the presence, size, and growth rate of peritumoral edema and cysts. Findings were compared with clinical symptoms using the Fisher exact test. RESULTS: We observed a total of 77 spinal hemangioblastomas in 28 patients. Eight of the 28 patients showed peritumoral edema and spinal cysts, and 1 patient showed peritumoral edema without cyst formation; 6 of these 9 patients showed clinical symptoms. Both peritumoral edema and spinal cysts were associated with clinical symptoms (P = 0.023 and P = 0.011, respectively). CONCLUSIONS: The presence of peritumoral edema and/or spinal cysts shown on MRI in VHL patients with spinal hemangioblastomas is associated with symptoms in more than half of the patients and may alert the clinician to intensify clinical and radiologic surveillance.

Intracranial aneurysm wall enhancement as an indicator of instability: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Aneurysm wall enhancement (AWE) of intracranial aneurysms on magnetic resonance imaging has been described in previous studies as a surrogate marker of instability. With this study, an updated literature overview and summary risk estimates of the association between AWE and different specific outcomes (i.e., rupture, growth or symptomatic presentation) for both cross-sectional and longitudinal studies are provided. METHODS: The PRISMA guideline was followed and a search was performed of PubMed and Embase to 1 January 2021 for studies that reported on AWE and aneurysm instability. In cross-sectional studies, AWE was compared between patients with stable and unstable aneurysms. In longitudinal studies, AWE of stable aneurysms was assessed at baseline after which patients were followed longitudinally. Risk ratios were calculated for longitudinal studies, prevalence ratios for cross-sectional studies and then the ratios were pooled in a random-effects meta-analysis. Also, the performance of AWE to differentiate between stable and unstable aneurysms was evaluated. RESULTS: Twelve studies were included with a total of 1761 aneurysms. In cross-sectional studies, AWE was positively associated with rupture (prevalence ratio 11.47, 95% confidence interval [CI] 4.05-32.46) and growth or symptomatic presentation (prevalence ratio 4.62, 95% CI 2.85-7.49). Longitudinal studies demonstrated a positive association between AWE and growth or rupture (risk ratio 8.00, 95% CI 2.14-29.88). Assessment of the performance of AWE showed high sensitivities, mixed specificities, low positive predictive values and high negative predictive values. CONCLUSIONS: Although AWE is positively associated with aneurysm instability, current evidence mostly supports the use of its absence as a surrogate marker of aneurysm stability.

Spinal Cord Ischemia Related to Disc Herniation: Case Report and a Review of the Literature.

Symptoms of spinal cord ischemia can mimic myelopathy due to spinal cord compression in the acute phase. Thoracic disc herniation with limited spinal cord compression but rapid progression of neurological symptoms causes a clinical dilemma as to whether emergency decompression should be performed. We report a case of acute progressive myelopathy due to spinal cord ischemia related to thoracic disc herniation initially managed by Th8 laminectomy with reduction of the herniated disc. Repeat imaging showed T2-weighted hyperintensity in the posterior cord. The clinical and radiological course supports posterior spinal artery ischemia. This case illustrates and a review of the literature shows that thoracic disc herniation may be complicated by ischemic myelopathy even in the absence of cord compression.

Paraneoplastic tumefactive demyelination with underlying combined germ cell cancer.

Paraneoplastic demyelination is a rare disorder of the central nervous system. We describe a 60-year-old man with tumefactive demyelination who had an underlying retroperitoneal germ cell cancer. He presented with visuospatial problems and memory loss and had a visual field defect. His MRI was interpreted as a glioma but stereotactic biopsy showed active demyelination. Investigation for multiple sclerosis was negative but CT imaging showed retroperitoneal lymphadenopathy, and nodal biopsy confirmed a combined germ cell cancer. He responded poorly to corticosteroid treatment, and his visual field defect progressed. However, 6 months after plasma exchange and successful chemotherapy, he has partially improved clinically and radiographically. Tumefactive demyelination is typically associated with multiple sclerosis but may be paraneoplastic. It is important to recognise paraneoplastic tumefactive demyelination early, as the neurological outcome relies on treating the associated malignancy.

Brain atrophy and cognition: interaction with cerebrovascular pathology?

We examined the interaction of brain atrophy and white matter lesions (WML) with cognitive functioning in 605 patients (mean age, 58±10; 76% men) with atherosclerotic disease from the Second Manifestations of ARTerial disease-MR substudy (SMART-MR study). Automated brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid, and WML on MRI. Total brain, ventricular, and cortical gray matter volume were divided by intracranial volume (ICV). Neuropsychological tests assessing executive functioning and memory performance were performed and composite scores were calculated. We observed that smaller total brain volume, larger ventricular volume, and smaller cortical gray matter volume (all as % of ICV) were associated with worse executive performance and that this association became stronger with presence of brain infarcts or severe WML volume (P-values for interaction <0.05). No interaction between measures of brain volume and cerebrovascular pathology on memory performance was observed. Our findings suggest that patients with cerebrovascular pathology on MRI may be more vulnerable to impairment in executive functioning related to global as well as focal brain atrophy.

White matter lesions and lacunar infarcts are independently and differently associated with brain atrophy: the SMART-MR study.

OBJECTIVE: To investigate the independent association of white matter lesions (WML) and lacunar infarcts (LI) with measures of global brain atrophy on MRI. METHODS: Within the SMART-MR study, a cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 840 patients (mean age 58 +/- 10 years, 80% male) without cortical, large subcortical or infratentorial infarcts. Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid and WML. Total brain volume, ventricular volume and cortical gray matter volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), ventricular fraction (VF) and cortical gray matter fraction (GMF). Location and number of infarcts were rated visually. RESULTS: Mean +/- SD BPF was 79.3 +/- 2.8%, mean +/- SD VF was 2.01 +/- 0.95%, and mean +/- SD GMF was 36.6 +/- 3.3%. Linear regression analyses, adjusted for age, sex, vascular risk factors, intima media thickness and LI showed that in patients with moderate to severe WML (upper quartile) BPF was lower (-0.51%; 95% CI -0.93 to -0.08%), VF was higher (0.48%; 95% CI 0.31-0.65%) and GMF was lower (-1.48%; 95% CI -2.07 to -0.88%) than in patients with few WML (lower quartile). Presence of LI was associated with lower BPF (-0.52%; 95% CI -0.96 to -0.07%) and higher VF (0.25%; 95% CI 0.07-0.42%), but not with GMF, independent of WML and other potential confounders. CONCLUSION: WML are associated with total, subcortical and cortical brain atrophy, whereas LI are associated with total and subcortical atrophy, but not with cortical atrophy, suggesting an independent role for WML and LI in the pathogenesis of brain atrophy.

Brain volumes and cerebrovascular lesions on MRI in patients with atherosclerotic disease. The SMART-MR study.

OBJECTIVE: To estimate brain volumes, white matter lesion (WML) volume and asymptomatic infarcts on MRI in a large cohort of patients with atherosclerotic disease. METHODS: Within the SMART-MR (Second Manifestations of ARTerial disease-Magnetic Resonance) study, a prospective cohort study on determinants and course of brain changes on MRI, cross-sectional analyses were performed in 1044 patients (mean age 58+/-10 years, 80% male) with coronary artery disease, cerebrovascular disease, peripheral arterial disease, or abdominal aortic aneurysm. Brain segmentation was used to quantify volumes of cortical gray matter, white matter, sulcal and ventricular cerebrospinal fluid, and WML. All volumes were expressed relative to intracranial volume. Brain infarcts were rated visually and distinctions were made between cortical infarcts, large subcortical infarcts, lacunar infarcts, and infarcts in the cerebellum and brainstem. RESULTS: With older age a nonlinear (quadratic) decrease in total brain volume was observed and a nonlinear increase in ventricular volume and WML. Cortical gray matter volume showed a linear decrease with age and was stronger in men than in women. WML volumes also increased more strongly in men than in women, while ventricular volume decrease showed no sex difference. Silent brain infarcts were present in 14% of men and women, and increased to 24% of subjects aged 65 years or older. CONCLUSION: In a population with atherosclerotic diseases, decrease in brain volumes with increasing age is comparable with findings from the general population. However, vascular pathology on MRI, as indicated by white matter lesions and silent brain infarcts may be more common.

Association of white matter lesions and lacunar infarcts with executive functioning: the SMART-MR study.

The authors investigated the association of white matter lesions and lacunar infarcts with cognitive performance and whether brain atrophy mediates these associations. Within the Second Manifestations of Arterial Disease-Magnetic Resonance study (2001-2005, the Netherlands), cross-sectional analyses of 522 patients were performed (mean age, 57 years (standard deviation, 10); 76% male). Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid, and white matter lesions. Infarcts were rated visually. Brain volume, ventricular volume, and gray matter volume were divided by intracranial volume to obtain indicators of brain atrophy. Neuropsychological tests assessing executive functioning and memory were performed, and scores were transformed into z scores. The authors used linear regression analyses, adjusted for age, sex, education, intelligence, and vascular risk factors, to investigate the association of white matter lesions and number of lacunar infarcts with cognitive performance. A 1-standard-deviation higher volume of white matter lesions (beta = -0.12, 95% confidence interval: -0.20, -0.04) and the presence of >or=2 lacunar infarcts (beta = -0.48, 95% confidence interval: -0.87, -0.09) were associated with worse executive functioning. These associations remained after adjusting for brain atrophy. Both were not associated with worse memory. Results suggest that subcortical ischemic vascular lesions are associated with decreased executive functioning, but not with memory functioning, independent of brain atrophy.

White matter lesions and brain atrophy: more than shared risk factors? A systematic review.

BACKGROUND: White matter lesions (WML) and brain atrophy are often found on MRI in the elderly. Shared vascular risk factors may be an explanation for their concomitance. However, disturbances of white matter integrity could also be involved in the pathogenesis of brain atrophy. Our objective was to systematically review studies that investigated the relation between WML and brain atrophy on MRI, and to investigate whether there is sufficient evidence to indicate that this relation is independent of shared risk factors. METHODS: We searched PubMed for studies published in English between 1980 and October 2007, combining search terms for WML and brain atrophy. Articles that studied the relation between WML and brain atrophy were included if they met the following criteria: (1) original study, (2) MRI used for imaging, (3) assessment methods for WML and brain atrophy specified, and (4) a sample size of at least 20 participants. We recorded type and age of the study population, type and assessment of WML and brain atrophy, and variables for which adjustments were made in the analyses. RESULTS: We identified 48 studies that met our inclusion criteria. A significant relation between WML and brain atrophy was found in 37 out of 48 studies. The source of the study population (e.g. clinic or population based) did not affect this relation. However, only 10 studies adjusted for shared risk factors, of which 9 found an association. CONCLUSIONS: The majority of studies found an association between WML and brain atrophy, but it is not yet clear if this association is independent of shared risk factors.

Visual rating of the hippocampus in non-demented elders: Does it measure hippocampal atrophy or other indices of brain atrophy? The SMART-MR study.

Visual rating of hippocampal atrophy is often used to differentiate between normal aging and Alzheimer's disease. We investigated whether two visual rating scales of hippocampal atrophy were related to hippocampal volumes, and if visual rating was related to global, cortical and subcortical brain atrophy in persons without dementia. Within the SMART-MR study, a prospective cohort study among patients with manifest arterial disease, medial temporal lobe atrophy was qualitatively rated in 95 participants without dementia (mean age 62 +/- 10 years) using two visual rating scales: the medial temporal lobe (MTA) score was rated on coronal oriented images and the perihippocampal cerebrospinal fluid (HCSF) score was rated on axial oriented images. Hippocampal volume assessed by manual segmentation on a 3-dimensional FFE T1-weighted MR image. Automated segmentation was used to quantify volumes of brain tissue and cerebrospinal fluid. Total brain volume, gray matter volume, and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF), gray matter fraction (GMF) and ventricular fraction (VF). Using ANOVA, crude hippocampal volumes were smaller with increasing MTA and HSCF scores as were hippocampal volumes normalized for intracranial volume (P < 0.05). However, hippocampal volumes normalized for total brain size were not smaller with increasing MTA or HSCF scores (P = 0.33 and P = 0.49). Also, with increasing visual rating scores, BPF was smaller and VF was larger (P < 0.001), and the GMF decreased with increasing HCSF score (P = 0.008). In this nondemented population, visual rating of the medial temporal lobe reflects hippocampal atrophy as well as global and subcortical atrophy.

Diabetes increases atrophy and vascular lesions on brain MRI in patients with symptomatic arterial disease.

BACKGROUND AND PURPOSE: Diabetes type 2 (DM2) is associated with accelerated cognitive decline and structural brain abnormalities. Macrovascular disease has been described as a determinant for brain MRI changes in DM2, but little is known about the involvement of other DM2-related factors. METHODS: Brain MRI was performed in 1043 participants (151 DM2) with symptomatic arterial disease. Brain volumes were obtained through automated segmentation. RESULTS: Patients with arterial disease and DM2 had more global and subcortical brain atrophy (-1.20% brain/intracranial volume [95%CI -1.58 to -0.82], P<0.0005 and 0.20% ventricular/intracranial volume [0.05 to 0.34], P<0.01), larger WMH volumes (0.22 logtransformed volume [0.07 to 0.38], P<0.005), and more lacunar infarcts (OR 1.75 [1.13 to 2.69], P<0.01) than identical patients without DM2. In patients with DM2, high glucose levels (B-0.12% per mmol/L [-0.23 to -0.01], P<0.05) and diabetes duration (B-0.05% per year [-0.10 to -0.001], P<0.05) were associated with global brain atrophy. CONCLUSIONS: In patients with symptomatic arterial disease, DM2 has an added detrimental effect on the brain. In patients with DM2, hyperglycemia and diabetes duration contribute to brain atrophy.

Total cerebral blood flow, white matter lesions and brain atrophy: the SMART-MR study.

We investigated whether total cerebral blood flow (CBF) was associated with brain atrophy, and whether this relation was modified by white matter lesions (WML). Within the Second Manifestations of ARTerial disease-magnetic resonance (SMART-MR) study, a prospective cohort study among patients with arterial disease, cross-sectional analyses were performed in 828 patients (mean age 58+/-10 years, 81% male) with quantitative flow, atrophy, and WML measurements on magnetic resonance imaging (MRI). Total CBF was measured with MR angiography and was expressed per 100 mL brain volume. Total brain volume and ventricular volume were divided by intracranial volume to obtain brain parenchymal fraction (BPF) and ventricular fraction (VF). Lower BPF indicates more global brain atrophy, whereas higher VF indicates more subcortical brain atrophy. Mean CBF was 52.0+/-10.2 mL/min per 100 mL, mean BPF was 79.2+/-2.9%, and mean VF was 2.03+/-0.96%. Linear regression analyses showed that lower CBF was associated with more subcortical brain atrophy, after adjusting for age, sex, vascular risk factors, intima-media thickness, and lacunar infarcts, but only in patients with moderate to severe WML (upper quartile of WML): Change in VF per s.d. decrease in CBF 0.18%, 95% CI: 0.02 to 0.34%. Our findings suggest that cerebral hypoperfusion in the presence of WML may be associated with subcortical brain atrophy.

Arterial blood flow to the brain in patients with vascular disease: the SMART Study.

PURPOSE: To retrospectively investigate which characteristics are related to total arterial blood flow to the brain in patients with symptomatic vascular disease. MATERIALS AND METHODS: The study was approved by the ethics committee of the authors' institution, and written informed consent was obtained. The total volume flow rate (tVFR) values in the internal carotid arteries and the basilar artery in 636 patients (536 men, 100 women; mean age, 58 years) with symptomatic vascular disease were measured with two-dimensional phase-contrast magnetic resonance (MR) angiography. Reference tVFR values in the general population were obtained from previous research involving 158 subjects (73 men, 85 women; mean age, 60 years). RESULTS: A higher tVFR was found in patients with symptomatic vascular disease, but this association was statistically significant in only those patients in the 7th decade of life. The mean tVFR decreased with increasing age (-3.4 mL/min per year; 95% confidence interval [CI]: -4.3, -2.5). Diabetes (-27.6 mL/min; 95% CI: -52.6, -2.6) and increasing body mass index (BMI) (-2.8 mL/min per BMI unit; 95% CI: -5.3, -0.2) were associated with lower tVFR. Patients with vascular disease in a cerebral location had lower tVFR values (-39.7 mL/min; 95% CI: -65.1, -14.3) than did patients with symptomatic vascular disease elsewhere in the vascular tree. CONCLUSION: Patients with symptomatic vascular disease had slightly higher arterial blood flow to the brain compared with the general population. The tVFR decreased with increasing age and increasing BMI, and patients with diabetes had lower tVFR values than did those without diabetes. Patients with vascular disease in a cerebral location had lower tVFR values than did those with symptomatic vascular disease at other arterial sites.