We performed a systematic review and meta-analysis on prospective studies that provided risk estimates for the impact of 3 different MRI markers of small vessel disease (SVD), namely white matter... Show moreWe performed a systematic review and meta-analysis on prospective studies that provided risk estimates for the impact of 3 different MRI markers of small vessel disease (SVD), namely white matter hyperintensities (WMH), cerebral microbleeds (CMB) and lacunes, on cognitive decline in relatively healthy older adults without cognitive deficits at baseline. A total of 23 prospective studies comprising 11,486 participants were included for analysis. Extracted data was pooled, reviewed and meta-analysed separately for global cognition, executive function, memory and attention. The pooled effect size for the association between cerebral SVD and cognitive decline was for global cognition -0.10 [-0.14; -0.05], for executive functioning -0.18 [-0.24; - 0.11], for memory -0.12 [-0.17; -0.07], and for attention -0.17 [-0.23; -0.11]. Results for the association of individual MRI markers of cerebral SVD were statistically significant for WMH and global cognition -0.15 [-0.24; -0.06], WMH and executive function -0.23 [-0.33; -0.13], WMH and memory -0.19 [-0.29; -0.09], WMH and attention -0.24 [-0.39; -0.08], CMB and executive function -0.07 [-0.13; -0.02], CMB and memory -0.11 [-0.21; -0.02] and CMB and attention -0.13 [-0.25; -0.02]. In conclusion, presence of MRI markers of cerebral SVD were found to predict an increased risk of cognitive decline in relatively healthy older adults. While WMH were found to significantly affect all cognitive domains, CMB influenced decline in executive functioning over time as well as (in some studies) decline in memory and attention. Show less
Kuijper, E.C.; Overzier, M.; Suidgeest, E.; Dzyubachyk, O.; Maguin, C.; Pérot, J.B.; ... ; Roon-Mom, W. van 2023
In Huntington disease, cellular toxicity is particularly caused by toxic protein fragments generated from the mutant huntingtin (HTT) protein. By modifying the HTT protein, we aim to reduce... Show moreIn Huntington disease, cellular toxicity is particularly caused by toxic protein fragments generated from the mutant huntingtin (HTT) protein. By modifying the HTT protein, we aim to reduce proteolytic cleavage and ameliorate the consequences of mutant HTT without lowering total HTT levels. To that end, we use an antisense oligonucleotide (AON) that targets HTT pre-mRNA and induces partial skipping of exon 12, which contains the critical caspase-6 cleavage site. Here, we show that AON-treatment can partially restore the phenotype of YAC128 mice, a mouse model expressing the full-length human HTT gene including 128 CAG-repeats. Wild-type and YAC128 mice were treated intracerebroventricularly with AON12.1, scrambled AON or vehicle starting at 6 months of age and followed up to 12 months of age, when MRI was performed and mice were sacrificed. AON12.1 treatment induced around 40% exon skip and protein modification. The phenotype on body weight and activity, but not rotarod, was restored by AON treatment. Genes differentially expressed in YAC128 striatum changed toward wild-type levels and striatal volume was preserved upon AON12.1 treatment. However, scrambled AON also showed a restorative effect on gene expression and appeared to generally increase brain volume. Show less
Hollander, N.K. den; Helm-van Mil, A.H.M. van der; Steenbergen, H.W. van 2023
ObjectiveObesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in... Show moreObjectiveObesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in detail from MRI-detected synovitis and osteitis to MRI-detected erosive progression, which precedes radiographic progression. Previous research suggested obesity associates with less osteitis and synovitis. We therefore aimed to (i) validate the previously suggested association between BMI and MRI-detected osteitis/synovitis; (ii) study whether this is specific for ACPA-positive or ACPA-negative RA or also present in other arthritides; (iii) study whether MRI-detected osteitis associates with MRI-detected erosive progression; and (iv) study whether obesity associates with MRI-detected erosive progression.MethodsWe studied 1029 early arthritis patients (454 RA, 575 other arthritides), consecutively included in Leiden Early Arthritis Clinic. At baseline patients underwent hand-and-foot MRI that were RAMRIS-scored, and 149 RA patients underwent follow-up MRIs. We studied associations between baseline BMI and MRI-detected osteitis/synovitis (using linear regression), and erosive progression (using Poisson mixed models).ResultsIn RA, higher BMI associated with less osteitis at disease onset (β = 0.94; 95% CI: 0.93, 0.96) but not with synovitis. Higher BMI associated with less osteitis in ACPA-positive RA (β = 0.95; 95% CI: 0.93, 0.97), ACPA-negative RA (β = 0.97; 95% CI: 0.95, 0.99) and other arthritides (β = 0.98; 95% CI: 0.96, 0.99). Over 2 years, overweight and obesity associated with less MRI-detected erosive progression (P = 0.02 and 0.03, respectively). Osteitis also associated with erosive progression over 2 years (P < 0.001).ConclusionsHigh BMI relates to less osteitis at disease onset, which is not confined to RA. Within RA, high BMI and less osteitis associated with less MRI-detected erosive progression. This suggests that the protective effect of obesity on radiographic progression is exerted via a path of less osteitis and subsequently fewer MRI-detected erosions. Show less
Zande, N.A. van de; Bulk, M.; Najac, C.; Weerd, L. van der; Bresser, J. de; Lewerenz, J.; ... ; Bot, S.T. de 2023
IntroductionStrong evidence suggests a significant role for iron accumulation in the brain in addition to the well-documented neurodegenerative aspects of Huntington’s disease (HD). The putative... Show moreIntroductionStrong evidence suggests a significant role for iron accumulation in the brain in addition to the well-documented neurodegenerative aspects of Huntington’s disease (HD). The putative mechanisms by which iron is linked to the HD pathogenesis are multiple, including oxidative stress, ferroptosis and neuroinflammation. However, no previous study in a neurodegenerative disease has linked the observed increase of brain iron accumulation as measured by MRI with well-established cerebrospinal fluid (CSF) and blood biomarkers for iron accumulation, or with associated processes such as neuroinflammation. This study is designed to link quantitative data from iron levels and neuroinflammation metabolites obtained from 7T MRI of HD patients, with specific and well-known clinical biofluid markers for iron accumulation, neurodegeneration and neuroinflammation. Biofluid markers will provide quantitative measures of overall iron accumulation, neurodegeneration and neuroinflammation, while MRI measurements on the other hand will provide quantitative spatial information on brain pathology, neuroinflammation and brain iron accumulation, which will be linked to clinical outcome measures.MethodsThis is an observational cross-sectional study, IMAGINE-HD, in HD gene expansion carriers and healthy controls. We include premanifest HD gene expansion carriers and patients with manifest HD in an early or moderate stage. The study includes a 7T MRI scan of the brain, clinical evaluation, motor, functional, and neuropsychological assessments, and sampling of CSF and blood for the detection of iron, neurodegenerative and inflammatory markers. Quantitative Susceptibility Maps will be reconstructed using T2* weighted images to quantify brain iron levels and Magnetic Resonance Spectroscopy will be used to obtain information about neuroinflammation by measuring cell-specific intracellular metabolites’ level and diffusion. Age and sex matched healthy subjects are included as a control group.DiscussionResults from this study will provide an important basis for the evaluation of brain iron levels and neuroinflammation metabolites as an imaging biomarker for disease stage in HD and their relationship with the salient pathomechanisms of the disease on the one hand, and with clinical outcome on the other. Show less
Rodrigues-Manica, S.; Sepriano, A.; Ramiro, S.; Landewe, R.; Claudepierre, P.; Molto, A.; ... ; Heijde, D. van der 2023
Objective: To assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to... Show moreObjective: To assess whether the presence of bone marrow edema (BME) leads to the development of structural lesions at the same anatomical location of the sacroiliac joints (SIJ), and to investigate the association between BME patterns over time and structural lesions in patients with early axial spondyloarthritis (axSpA). Methods: Patients with axSpA from the DESIR cohort with & GE;2 consecutive magnetic resonance imaging (MRI)-SIJ were assessed at baseline, 2 and 5 years. MRI-SIJ images were divided into 8 quadrants. The association between BME and subsequent structural lesions (sclerosis, erosions, fatty lesions, and ankylosis) on MRI in the same quadrant was tested longitudinally. Additionally, patients were grouped according to the pattern of BME evo-lution across quadrants over time (no BME, sporadic, fluctuating, and persistent). The association between these patterns and 5-year imaging outcomes (eg: & GE;5 erosions and/or fatty lesions on MRI-SIJ) was tested. Results: In total, 196 patients were included. BME in each quadrant was associated with sclerosis (OR:1.9 (95%CI: 1.1;3.4)), erosions (1.9 (1.5;2.5)) and fatty lesions (1.9 (1.4;2.6)). Ankylosis was uncommon. There was a gradient between increased level of inflammation and subsequent damage: compared to the 'no BME' pattern, the sporadic (OR (95% CI): 2.1 (1.0;4.5)), fluctuating (OR:5.6(2.2;14.4)) and persistent (OR:7.5(2.8;19.6)) patterns were associated with higher structural damage on MRI-SIJ at 5-years. Conclusions: In early axSpA, inflammation on MRI-SIJ leads to damage at the quadrant level. The higher the exposure to inflammation across quadrants in the SIJs over time the higher the likelihood of subsequent struc-tural damage, suggesting a cumulative effect. Show less
Background: The cause of sudden sensorineural hearing loss (SSNHL) is uncertain in a significant number of patients. A vascular etiology has been proposed because SSNHL increases the risk of... Show moreBackground: The cause of sudden sensorineural hearing loss (SSNHL) is uncertain in a significant number of patients. A vascular etiology has been proposed because SSNHL increases the risk of developing a stroke. Cardiovascular risk factors can cause cerebral small vessel disease (CSVD). The presence of CSVD in turn raises the risk of stroke. Aim: The aim of this study was to compare the presence of CSVD and cardiovascular risk factors in elderly patients with idiopathic SSNHL (iSSNHL) to a control cohort. Method: Patients with iSSNHL of 50 years and older were compared with a control cohort with patients suspected of trigeminal neuralgia or vestibular paroxysmia. The primary outcome was the difference in the number of white matter hyperintensities using the ordinal Fazekas scale. Secondary outcomes were the presence of brain infarctions on MRI and the difference in cardiovascular risk factors. Results: In the SSNHL cohort, Fazekas score 2 was most frequently seen compared with Fazekas 1 in the control cohort. The distribution of Fazekas scores did not differ significantly. The sum of the Fazekas scores were 13,925 and 14,042 for iSSNHL and controls, respectively (p = 0.908). Brain infarctions were seen in 8 patients with iSSNHL (n = 118) and in 13 patients in the control cohort (n = 118) (p = 0.361). None of the cardiovascular risk factors were more frequently seen in the iSSNHL cohort. Conclusion: Patients with iSSNHL did not exhibit more CSVD on MRI than controls. This result is in contrast with previous literature demonstrating a higher risk of stroke in patients with iSSNHL than in controls. A prospective analysis with a larger study population is therefore warranted. Show less
Objectives:Renal sympathetic denervation (RDN) reduces blood pressure (BP). However, one out of three patients does not exhibit a significant BP response to the therapy. This study investigates the... Show moreObjectives:Renal sympathetic denervation (RDN) reduces blood pressure (BP). However, one out of three patients does not exhibit a significant BP response to the therapy. This study investigates the association between noninvasive vascular stiffness indices and RDN-mediated BP reduction.Methods:In this prospective, single-arm pilot study, patients with systolic office BP at least 140 mmHg, mean 24-h systolic ambulatory blood pressure (ABP) at least 130 mmHg and at least three prescribed antihypertensive drugs underwent radiofrequency RDN. The primary efficacy endpoint was temporal evolution of mean 24-h systolic ABP throughout 1-year post RDN (measured at baseline and 3-6-12 months). Effect modification was studied for baseline ultrasound carotid-femoral and magnetic resonance (MR) pulse wave velocity (PWV), MR aortic distensibility, cardiac MR left ventricular parameters and clinical variables. Statistical analyses were performed using linear mixed-effects models, and effect modification was assessed using interaction terms.Results:Thirty patients (mean age 62.5 +/- 10.7 years, 50% women) with mean 24-h ABP 146.7/80.8 +/- 13.7/12.0 mmHg were enrolled. Following RDN, mean 24-h systolic ABP changed with -8.4 (95% CI: -14.5 to -2.3) mmHg/year (P = 0.007). Independent effect modifiers were CF-PWV [+2.7 (0.3 to 5.1) mmHg/year change in outcome for every m/s increase in CF-PWV; P = 0.03], daytime diastolic ABP [-0.4 (-0.8 to 0.0) mmHg/year per mmHg; P = 0.03], age [+0.6 (0.2 to 1.0) mmHg/year per year of age; P = 0.006], female sex [-14.0 (-23.1 to -5.0) mmHg/year as compared with men; P = 0.003] and BMI [+1.2 (0.1 to 2.2) mmHg/year per kg/m(2); P = 0.04].Conclusion:Higher CF-PWV at baseline was associated with a smaller reduction in systolic ABP following RDN. These findings could contribute to improve identification of RDN responders. Show less
Objective: To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine... Show moreObjective: To investigate the test-retest precision and to report the longitudinal change in cartilage thickness, the percentage of knees with progression and the predictive value of the machine-learning-estimated structural progression score (s-score) for cartilage thickness loss in the IMI-APPROACH cohort - an exploratory, 5-center, 2-year prospective follow-up cohort. Design: Quantitative cartilage morphology at baseline and at least one follow-up visit was available for 270 of the 297 IMI-APPROACH participants (78% females, age: 66.4 +/- 7.1 years, body mass index (BMI): 28.1 +/- 5.3 kg/m(2), 55% with radiographic knee osteoarthritis (OA)) from 1.5T or 3T MRI. Test-retest precision (root mean square coefficient of variation) was assessed from 34 participants. To define progressor knees, smallest detectable change (SDC) thresholds were computed from 11 participants with longitudinal test-retest scans. Binary logistic regression was used to evaluate the odds of progression in femorotibial cartilage thickness (threshold: similar to 211 mu m) for the quartile with the highest vs the quartile with the lowest s-scores. Results: The test-retest precision was 69 mu m for the entire femorotibial joint. Over 24 months, mean cartilage thickness loss in the entire femorotibial joint reached -174 mu m (95% CI: [-207, -141] mu m, 32.7% with progression). The s-score was not associated with 24-month progression rates by MRI (OR: 1.30, 95% CI: [0.52, 3.28]). Conclusion: IMI-APPROACH successfully enrolled participants with substantial cartilage thickness loss, although the machine-learning-estimated s-score was not observed to be predictive of cartilage thickness loss. IMI-APPROACH data will be used in subsequent analyses to evaluate the impact of clinical, imaging, biomechanical and biochemical biomarkers on cartilage thickness loss and to refine the machine-learning-based s-score. (c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Jansen, M.P.; Roemer, F.W.; Marijnissen, A.K.C.A.; Kloppenburg, M.; Blanco, F.J.; Haugen, I.K.; ... ; Wirth, W. 2023
Objective: Longitudinal weight-bearing radiographic joint space width (JSW) and non-weight-bearing MRI-based cartilage thickness changes often show weak correlations. The current objective was to... Show moreObjective: Longitudinal weight-bearing radiographic joint space width (JSW) and non-weight-bearing MRI-based cartilage thickness changes often show weak correlations. The current objective was to investigate these correlations, and to explore the influence of different factors that could contribute to longitudinal differences between the two methods. Methods: The current study included 178 participants with medial osteoarthritis (OA) out of the 297 knee OA participants enrolled in the IMI-APPROACH cohort. Changes over 2 years in medial JSW (delta JSWmed), minimum JSW (delta JSWmin), and medial femorotibial cartilage thickness (delta MFTC) were assessed using linear regression, using measurements from radiographs and MRI acquired at baseline, 6 months, and 1 and 2 years. Pearson R correlations were calculated. The influence of cartilage quality (T2 mapping), meniscal extrusion (MOAKS scoring), potential pain-induced unloading (difference in knee specific pain scores), and increased loading (BMI) on the correlations was analyzed by dividing participants in groups based on each factor separately, and comparing correlations (slope and strength) between groups using linear regression models. Result: Correlations between delta MFTC and delta JSWmed and delta JSWmin were statistically significant (p < 0.004) but weak (R < 0.35). Correlations were significantly different between groups based on cartilage quality and on meniscal extrusion: only patients with the lowest T2 values and with meniscal extrusion showed significant moderate correlations. Pain-induced unloading or BMI-induced loading did not influence correlations.Conclusions: While the amount of loading does not seem to make a difference, weight-bearing radiographic JSW changes are a better reflection of non-weight-bearing MRI cartilage thickness changes in knees with higher quality cartilage and with meniscal extrusion. Show less
Zwartbol, M.H.T.; Ghaznawi, R.; Jaarsma-Coes, M.; Kuijf, H.; Hendrikse, J.; Bresser, J. de; ... ; UCC-SMART Study Grp 2022
White matter hyperintensity (WMH) shape has been associated with the severity of the underlying brain pathology, suggesting it is a potential neuroimaging marker of WMH impact on brain function.In... Show moreWhite matter hyperintensity (WMH) shape has been associated with the severity of the underlying brain pathology, suggesting it is a potential neuroimaging marker of WMH impact on brain function.In 563 patients with vascular disease (58 +/- 10 years), we examined the relationship between WMH volume, shape, and cognitive functioning. WMH volume and shape were automatically determined on 1.5T brain MRI data. Standardized linear regression analyses estimated the association between WMH volume and shape (concavity index, solidity, convexity, fractal dimension, and eccentricity) and memory and executive functioning, adjusted for age, sex, educational level, and reading ability.Larger WMH volumes were associated with lower executive functioning Z-scores ( b (95%-CI):-0.09 (-0.17;-0.01)). Increased shape complexity of periventricular/confluent WMH associated with lower exec-utive functioning (concavity index + 1SD:-0.13 (-0.20;-0.06); solidity-1SD:-0.09 (-0.17;-0.02)) and lower memory function (fractal dimension + 1SD:-0.10 (-0.18;-0.02)). Of note, the association between concav-ity index and executive functioning was independent of WMH volume (-0.12 (-0.19;-0.04)). Our results suggest that WMH shape contains additional information about WMH burden, not other-wise captured by WMH volume.(c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
Here, we describe the synthesis of a novel type of rare-earth-doped nanoparticles (NPs) for multimodal imaging, by combining the rare-earth elements Ce, Gd and Nd in a crystalline host lattice... Show moreHere, we describe the synthesis of a novel type of rare-earth-doped nanoparticles (NPs) for multimodal imaging, by combining the rare-earth elements Ce, Gd and Nd in a crystalline host lattice consisting of CaF2 (CaF2: Ce, Gd, Nd). CaF2: Ce, Gd, Nd NPs are small (15-20 nm), of uniform shape and size distribution, and show good biocompatibility and low immunogenicity in vitro. In addition, CaF2: Ce, Gd, Nd NPs possess excellent optical properties. CaF2: Ce, Gd, Nd NPs produce downconversion emissions in the second near-infrared window (NIR-II, 1000-1700 nm) under 808 nm excitation, with a strong emission peak at 1056 nm. Excitation in the first near- infrared window (NIR-I, 700-900 nm) has the advantage of deeper tissue penetration power and reduced autofluorescence, compared to visible light. Thus, CaF2: Ce, Gd, Nd NPs are ideally suited for in vivo fluorescence imaging. In addition, the presence of Gd3+ makes the NPs intrinsically monitorable by magnetic resonance imaging (MRI). Moreover, next to fluorescence and MR imaging, our results show that CaF2: Ce, Gd, Nd NPs can be used as imaging probes for photoacoustic imaging (PAI) in vitro. Therefore, due to their biocompatibility and suitability as multimodal imaging probes, CaF2: Ce, Gd, Nd NPs exhibit great potential as a traceable imaging agent in biomedical applications. Show less
Roemer, F.W.; Jansen, M.; Marijnissen, A.C.A.; Guermazi, A.; Heiss, R.; Maschek, S.; ... ; Wirth, W. 2022
Background: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI... Show moreBackground: The IMI-APPROACH cohort is an exploratory, 5-centre, 2-year prospective follow-up study of knee osteoarthritis (OA). Aim was to describe baseline multi-tissue semiquantitative MRI evaluation of index knees and to describe change for different MRI features based on number of subregion-approaches and change in maximum grades over a 24-month period.Methods: MRIs were acquired using 1.5 T or 3 T MRI systems and assessed using the semi-quantitative MRI OA Knee Scoring (MOAKS) system. MRIs were read at baseline and 24-months for cartilage damage, bone marrow lesions (BML), osteophytes, meniscal damage and extrusion, and Hoffa- and effusion-synovitis. In descriptive fashion, the frequencies of MRI features at baseline and change in these imaging biomarkers over time are presented for the entire sample in a subregional and maximum score approach for most features. Differences between knees without and with structural radiographic (R) OA are analyzed in addition.Results: Two hundred eighty-nine participants had readable baseline MRI examinations. Mean age was 66.6 +/- 7.1 years and participants had a mean BMI of 28.1 +/- 5.3 kg/m(2). The majority (55.3%) of included knees had radiographic OA. Any change in total cartilage MOAKS score was observed in 53.1% considering full-grade changes only, and in 73.9% including full-grade and within-grade changes. Any medial cartilage progression was seen in 23.9% and any lateral progression on 22.1%. While for the medial and lateral compartments numbers of subregions with improvement and worsening of BMLs were very similar, for the PFJ more improvement was observed compared to worsening (15.5% vs. 9.0%). Including within grade changes, the number of knees showing BML worsening increased from 42.2% to 55.6%. While for some features 24-months change was rare, frequency of change was much more common in knees with vs. without ROA (e.g. worsening of total MOAKS score cartilage in 68.4% of ROA knees vs. 36.7% of no-ROA knees, and 60.7% vs. 21.8% for an increase in maximum BML score per knee).Conclusions: A wide range of MRI-detected structural pathologies was present in the IMI-APPROACH cohort. Baseline prevalence and change of features was substantially more common in the ROA subgroup compared to the knees without ROA. Show less
Custers, P.A.; Maas, M.; Lambregts, D.M.J.; Beets-Tan, R.G.H.; Beets, G.L.; Peters, F.P.; ... ; Triest, B. van 2022
Simple Summary: Contact X-ray brachytherapy (CXB) after neoadjuvant (chemo)radiotherapy for rectal cancer is applied in selected patients aiming at organ preservation. However, limited data exist... Show moreSimple Summary: Contact X-ray brachytherapy (CXB) after neoadjuvant (chemo)radiotherapy for rectal cancer is applied in selected patients aiming at organ preservation. However, limited data exist on features observed on endoscopy and MRI after treatment with CXB. On endoscopy, features observed in most patients 6 months after CXB are a flat, white scar, indicative for a clinical complete response (cCR), or tumor mass. On MRI, features indicative for a residual tumor are a focal tumor signal on T2W-MRI and a mass-like high signal on DWI. Due to treatment-related features observed early in follow-up, an irregular ulcer on endoscopy and a diffuse "reactive" mucosal signal on DWI, the distinction between a cCR and a residual tumor generally can be made at 6 months of follow-up. These results can help clinicians to interpret imaging features following CXB, ultimately, to identify patients with a cCR for Watch-and-Wait and to identify patients with a residual tumor for subsequent total mesorectal excision. After neoadjuvant (chemo)radiotherapy for rectal cancer, contact X-ray brachytherapy (CXB) can be applied aiming at organ preservation. This explorative study describes the early features on endoscopy and MRI after CXB. Patients treated with CXB following (chemo)radiotherapy and a follow-up of >= 12 months were selected. Endoscopy and MRI were performed every 3 months. Expert readers scored all the images according to structured reporting templates. Thirty-six patients were included, 15 of whom obtained a cCR. On endoscopy, the most frequently observed feature early in follow-up was an ulcer, regardless of whether patients developed a cCR. A flat, white scar and tumor mass were common at 6 months. Focal tumor signal on T2W-MRI and mass-like high signal on DWI were generally absent in patients with a cCR. An ulceration on T2W-MRI and "reactive" mucosal signal on DWI were observed early in follow-up regardless of the final tumor response. The distinction between a cCR and a residual tumor generally can be made at 6 months. Features associated with a residual tumor are tumor mass on endoscopy, focal tumor signal on T2W-MRI, and mass-like high signal on DWI. Early recognition of these features is necessary to identify patients who will not develop a cCR as early as possible. Show less
BackgroundIn multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (PanNETs) have a high prevalence and represent the main cause of death. This study aimed to assess the... Show moreBackgroundIn multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (PanNETs) have a high prevalence and represent the main cause of death. This study aimed to assess the diagnostic accuracy of the currently used conventional pancreatic imaging techniques and the added value of fine needle aspirations (FNAs). MethodsPatients who had at least one imaging study were included from the population-based MEN1 database of the DutchMEN Study Group from 1990 to 2017. Magnetic resonance imaging (MRI), computed tomography (CT), endoscopic ultrasonography (EUS), FNA, and surgical resection specimens were obtained. The first MRI, CT, or EUS was considered as the index test. For a comparison of the diagnostic accuracy of MRI versus CT, patients with their index test taken between 2010 and 2017 were included. The reference standard consisted of surgical histopathology or radiological follow-up. ResultsA total of 413 patients (92.8% of the database) underwent 3,477 imaging studies. The number of imaging studies per patient increased, and a preference for MRI was observed in the last decade. Overall diagnostic accuracy was good with a positive (PPV) and negative predictive value (NPV) of 88.9% (95% confidence interval, 76.0-95.6) and 92.8% (89.4-95.1), respectively, for PanNET in the pancreatic head and 92.0% (85.3-96.0) and 85.3% (80.5-89.1), respectively, in the body/tail. For MRI, PPV and NPV for pancreatic head tumors were 100% (76.1-100) and 87.1% (76.3-93.6) and for CT, 60.0% (22.9-88.4) and 70.4% (51.3-84.3), respectively. For body/tail tumors, PPV and NPV were 91.3% (72.0-98.8) and 87.0% (75.3-93.9), respectively, for MRI and 100% (74.9-100) and 77.8% (54.3-91.5), respectively, for CT. Pathology confirmed a PanNET in 106 out of 110 (96.4%) resection specimens. FNA was performed on 34 lesions in 33 patients and was considered PanNET in 24 [all confirmed PanNET by histology (10) or follow-up (14)], normal/cyst/unrepresentative in 6 (all confirmed PanNET by follow-up), and adenocarcinoma in 4 (2 confirmed and 2 PanNET). Three patients, all older than 60 years, had a final diagnosis of pancreatic adenocarcinoma. ConclusionAs the accuracy for diagnosing MEN1-related PanNET of MRI was higher than that of CT, MRI should be the preferred (non-invasive) imaging modality for PanNET screening/surveillance. The high diagnostic accuracy of pancreatic imaging and the sporadic occurrence of pancreatic adenocarcinoma question the need for routine (EUS-guided) FNA. Show less
Introduction: It has been hypothesized that carotid artery stenosis (CAS) may lead to greater atrophy of subserved brain regions; however, prospective studies on the impact of CAS on progression of... Show moreIntroduction: It has been hypothesized that carotid artery stenosis (CAS) may lead to greater atrophy of subserved brain regions; however, prospective studies on the impact of CAS on progression of hemispheric brain atrophy are lacking. We examined the association between CAS and progression of hemispheric brain atrophy. Methods: We included 654 patients (57 +/- 9 years) of the SMART-MR study, a prospective cohort study of patients with manifest arterial disease. Patients had baseline CAS duplex measurements and a 1.5T brain MRI at baseline and after 4 years of follow-up. Mean change in hemispheric brain volumes (% of intracranial volume [ICV]) was estimated between baseline and follow-up for left-sided and right-sided CAS across three degrees of stenosis (mild [<= 29%], moderate [30-69%], and severe [>= 70%]), adjusting for demographics, cerebrovascular risk factors, and brain infarcts. Results: Mean decrease in left and right hemispheric brain volumes was 1.15% ICV and 0.82% ICV, respectively, over 4 years of follow-up. Severe right-sided CAS, compared to mild CAS, was associated with a greater decrease in volume of the left hemisphere (B = -0.49% ICV, 95% CI: -0.86 to -0.13) and more profoundly of the right hemisphere (B = -0.90% ICV, 95% CI: -1.27 to -0.54). This pattern was independent of cerebrovascular risk factors, brain infarcts, and white matter hyperintensities on MRI, and was also observed when accounting for the presence of severe bilateral CAS. Increasing degrees of left-sided CAS, however, was not associated with greater volume loss of the left or right hemisphere. Conclusions: Our data indicate that severe (>= 70%) CAS could represent a risk factor for greater ipsilateral brain volume loss, independent of cerebrovascular risk factors, brain infarcts, or white matter hyperintensities on MRI. Further longitudinal studies in other cohorts are warranted to confirm this novel finding. (C) 2022 The Author(s). Published by S. Karger AG, Basel Show less
Setroikromo, S.N.W.; Werff, S.J.A. van der; Smit, A.S.; Vermetten, E.; Wee, N.J.A. van der 2022
BackgroundInsights into the neurobiological basis of resilience can have important implications for the prevention and treatment of stress-related disorders, especially in populations that are... Show moreBackgroundInsights into the neurobiological basis of resilience can have important implications for the prevention and treatment of stress-related disorders, especially in populations that are subjected to high-stress environments. Evaluating large-scale resting-state networks (RSNs) can provide information regarding resilient specific brain function which may be useful in understanding resilience. This study aimed to explore functional connectivity patterns specific for (high) resilience in Dutch policemen after exposure to multiple work-related traumatic events. We investigated resting-state functional connectivity (RSFC) of the salience network (SN), limbic network, and the default-mode network (DMN). MethodsResting-state functional MRI scans were obtained from trauma-exposed executive personnel of the Dutch police force and non-trauma-exposed recruits from the police academy. Participants were divided into three groups: a resilient group (n = 31; trauma exposure; no psychopathology), a vulnerable group (n = 32; trauma exposure, psychopathology), and a control group (n = 19; no trauma exposure, no psychopathology). RSFC of the three networks of interest was compared between these groups, using an independent component analysis and a dual regression approach. ResultsWe found decreased resilience-specific positive RSFC of the salience network with several prefrontal regions. The DMN and limbic network RFSC did not show resilience-specific patterns. ConclusionThis study shows a differential RSFC specific for resilient police officers. This differential RSFC may be related to a greater capacity for internal-focused thought and interoceptive awareness, allowing more effective higher-order responses to stress in highly resilient individuals. Show less
Neve, O.M.; Chen, Y.J.; Tao, Q.; Romeijn, S.R.; Boer, N.P. de; Grootjans, W.; ... ; Staring, M. 2022
Purpose: To develop automated vestibular schwannoma measurements on contrast-enhanced T1- and T2-weighted MRI scans.Materials and Methods: MRI data from 214 patients in 37 different centers were... Show morePurpose: To develop automated vestibular schwannoma measurements on contrast-enhanced T1- and T2-weighted MRI scans.Materials and Methods: MRI data from 214 patients in 37 different centers were retrospectively analyzed between 2020 and 2021. Patients with hearing loss (134 positive for vestibular schwannoma [mean age 6 SD, 54 years 6 12; 64 men] and 80 negative for vestibular schwannoma) were randomly assigned to a training and validation set and to an independent test set. A convolutional neural network (CNN) was trained using fivefold cross-validation for two models (T1 and T2). Quantitative analysis, including Dice index, Hausdorff distance, surface-to-surface distance (S2S), and relative volume error, was used to compare the computer and the human delineations. An observer study was performed in which two experienced physicians evaluated both delineations.Results: The T1-weighted model showed state-of-the-art performance, with a mean S2S distance of less than 0.6 mm for the whole tumor and the intrameatal and extrameatal tumor parts. The whole tumor Dice index and Hausdorff distance were 0.92 and 2.1 mm in the independent test set, respectively. T2-weighted images had a mean S2S distance less than 0.6 mm for the whole tumor and the intrameatal and extrameatal tumor parts. The whole tumor Dice index and Hausdorff distance were 0.87 and 1.5 mm in the independent test set. The observer study indicated that the tool was similar to human delineations in 85%-92% of cases.Conclusion: The CNN model detected and delineated vestibular schwannomas accurately on contrast-enhanced T1- and T2-weighted MRI scans and distinguished the clinically relevant difference between intrameatal and extrameatal tumor parts. (C) RSNA, 2022 Show less
Outeiral, R.R.; Bos, P.; Hulst, H.J. van der; Al-Mamgani, A.; Jasperse, B.; Simoes, R.; Heide, U.A. van der 2022
Background and purpose: Contouring oropharyngeal primary tumors in radiotherapy is currently done manually which is time-consuming. Autocontouring techniques based on deep learning methods are a... Show moreBackground and purpose: Contouring oropharyngeal primary tumors in radiotherapy is currently done manually which is time-consuming. Autocontouring techniques based on deep learning methods are a desirable alternative, but these methods can render suboptimal results when the structure to segment is considerably smaller than the rest of the image. The purpose of this work was to investigate different strategies to tackle the class imbalance problem in this tumor site.Materials and methods: A cohort of 230 oropharyngeal cancer patients treated between 2010 and 2018 was retrospectively collected. The following magnetic resonance imaging (MRI) sequences were available: T1 -weighted, T2-weighted, 3D T1-weighted after gadolinium injection. Two strategies to tackle the class imbal-ance problem were studied: training with different loss functions (namely: Dice loss, Generalized Dice loss, Focal Tversky loss and Unified Focal loss) and implementing a two-stage approach (i.e. splitting the task in detection and segmentation). Segmentation performance was measured with Sorensen-Dice coefficient (Dice), 95th Hausdorff distance (HD) and Mean Surface Distance (MSD). Results: The network trained with the Generalized Dice Loss yielded a median Dice of 0.54, median 95th HD of 10.6 mm and median MSD of 2.4 mm but no significant differences were observed among the different loss functions (p-value > 0.7). The two-stage approach resulted in a median Dice of 0.64, median HD of 8.7 mm and median MSD of 2.1 mm, significantly outperforming the end-to-end 3D U-Net (p-value < 0.05).Conclusion: No significant differences were observed when training with different loss functions. The two-stage approach outperformed the end-to-end 3D U-Net. Show less
Background: Ageing is highly associated with cognitive decline and modifiable risk factors such as diet are believed to protect against this process. Specific dietary components and in particular, ... Show moreBackground: Ageing is highly associated with cognitive decline and modifiable risk factors such as diet are believed to protect against this process. Specific dietary components and in particular, (poly)phenol-rich fruits such as berries have been increasingly recognised for their protection against age-related neurodegeneration. However, the impact of cranberries on cognitive function and neural functioning in older adults remains unclear. Design: A 12-week parallel randomised placebo-controlled trial of freeze-dried cranberry powder was conducted in 60 older adults aged between 50 and 80 years. Cognitive assessment, including memory and executive function, neuroimaging and blood sample collection were conducted before and after the intervention to assess the impact of daily cranberry consumption on cognition, brain function and biomarkers of neuronal signalling. Results: Cranberry supplementation for 12 weeks was associated with improvements in visual episodic memory in aged participants when compared to placebo. Mechanisms of action may include increased regional perfusion in the right entorhinal cortex, the accumbens area and the caudate in the cranberry group. Significant decrease in low-density lipoprotein (LDL) cholesterol during the course of the intervention was also observed. No significant differences were, however, detected for BDNF levels between groups. Conclusions:The results of this study indicate that daily cranberry supplementation(equivalent to 1 small cup of cranberries) over a 12-week period improves episodicmemory performance and neural functioning, providing a basis for future investigationsto determine efficacy in the context of neurological disease. Show less
Background: Acute audiovestibular loss is a neurotologic emergency of which the etiology is frequently unknown. In vestibular neuritis a viral genesis is expected, although there is insufficient... Show moreBackground: Acute audiovestibular loss is a neurotologic emergency of which the etiology is frequently unknown. In vestibular neuritis a viral genesis is expected, although there is insufficient evidence to support viruses as the only possible etiological factor. In sudden deafness, a vascular etiology has been proposed in elderly patients, since cardiovascular risk factors are more frequently present and a higher risk of developing a stroke was seen compared to the general population. So far, very little research has been carried out on vascular involvement in elderly patients with vestibular neuritis. Cardiovascular risk factors have a positive correlation with cerebral small vessel disease, visible as white matter hyperintensities, brain infarctions, microbleeds and lacunes on MRI. The presence of these characteristics indicate a higher risk of developing a stroke. Aim: We investigated whether elderly patients with vestibular neuritis have a higher prevalence of vascular lesions on MRI compared to a control cohort. Materials and Methods: Patients of 50-years and older, diagnosed with vestibular neuritis in a multidisciplinary tertiary referral hospital, were retrospectively reviewed and compared to a control cohort. The primary outcome was the difference in cerebral small vessel disease on MRI imaging, which was assessed by the number of white matter hyperintensities using the ordinal Fazekas scale. Secondary outcomes were the presence of brain infarctions on MRI and the difference in cardiovascular risk factors. Results: Patients with vestibular neuritis (N = 101) had a 1.60 higher odds of receiving a higher Fazekas score than the control cohort (N = 203) (p = 0.048), there was no difference in presence of brain infarctions (p = 1.0). Hyperlipidemia and atrial fibrillation were more common in patients experiencing vestibular neuritis. Conclusion: We found a positive correlation of white matter hyperintensities and VN which supports the hypothesis of vascular involvement in the pathophysiology of vestibular neuritis in elderly patients. Further prospective research is necessary to confirm this correlation. Show less
