The aim of this study was to validate geometric accuracy and in vivo reproducibility of landmark-based cephalometric measurements using high-resolution 3D Magnetic Resonance Imaging (MRI) at 3 Tesla. ...For accuracy validation, 96 angular and 96 linear measurements were taken on a phantom in 3 different positions. In vivo MRI scans were performed on 3 volunteers in five head positions. For each in vivo scan, 27 landmarks were determined from which 19 angles and 26 distances were calculated. Statistical analysis was performed using Bland-Altman analysis, the two one-sided tests procedure and repeated measures one-way analysis of variance. In comparison to ground truth, all MRI-based phantom measurements showed statistical equivalence (p < 0.001) and an excellent agreement in Bland-Altman analysis (bias ranges: -0.090-0.044°, -0.220-0.241 mm). In vivo cephalometric analysis was highly reproducible among the five different head positions in all study participants, without statistical differences for all angles and distances (p > 0.05). Ranges between maximum and minimum in vivo values were consistently smaller than 2° and 2 mm, respectively (average ranges: 0.88°/0.87 mm). In conclusion, this study demonstrates that accurate and reproducible 3D cephalometric analysis can be performed without exposure to ionizing radiation using MRI.
Glioblastoma, the most common and aggressive primary brain tumor type, is considered an immunologically "cold" tumor with sparse infiltration by adaptive immune cells. Immunosuppressive ...tumor-associated myeloid cells are drivers of tumor progression. Therefore, targeting and reprogramming intratumoral myeloid cells is an appealing therapeutic strategy. Here, we investigate a β-cyclodextrin nanoparticle (CDNP) formulation encapsulating the Toll-like receptor 7 and 8 (TLR7/8) agonist R848 (CDNP-R848) to reprogram myeloid cells in the glioma microenvironment. We show that intravenous monotherapy with CDNP-R848 induces regression of established syngeneic experimental glioma, resulting in increased survival rates compared with unloaded CDNP controls. Mechanistically, CDNP-R848 treatment reshapes the immunosuppressive tumor microenvironment and orchestrates tumor clearing by pro-inflammatory tumor-associated myeloid cells, independently of T cells and NK cells. Using serial magnetic resonance imaging, we identify a radiomic signature in response to CDNP-R848 treatment and ultrasmall superparamagnetic iron oxide (USPIO) imaging reveals that immunosuppressive macrophage recruitment is reduced by CDNP-R848. In conclusion, CDNP-R848 induces tumor regression in experimental glioma by targeting blood-borne macrophages without requiring adaptive immunity.
Abstract
Neurofilament light chain (NfL), released during central nervous injury, has evolved as a powerful serum marker of disease severity in many neurological disorders, including infectious ...diseases. So far NfL has not been assessed in cerebral malaria in human or its rodent model experimental cerebral malaria (ECM), a disease that can lead to fatal brain edema or reversible brain edema. In this study we assessed if NfL serum levels can also grade disease severity in an ECM mouse model with reversible (n = 11) and irreversible edema (n = 10). Blood–brain-barrier disruption and brain volume were determined by magnetic resonance imaging. Neurofilament density volume as well as structural integrity were examined by electron microscopy in regions of most severe brain damage (olfactory bulb (OB), cortex and brainstem). NfL plasma levels in mice with irreversible edema (317.0 ± 45.01 pg/ml) or reversible edema (528.3 ± 125.4 pg/ml) were significantly increased compared to controls (103.4 ± 25.78 pg/ml) by three to five fold, but did not differ significantly in mice with reversible or irreversible edema. In both reversible and irreversible edema, the brain region most affected was the OB with highest level of blood–brain-barrier disruption and most pronounced decrease in neurofilament density volume, which correlated with NfL plasma levels (r = − 0.68, p = 0.045). In cortical and brainstem regions neurofilament density was only decreased in mice with irreversible edema and strongest in the brainstem. In reversible edema NfL plasma levels, MRI findings and neurofilament volume density normalized at 3 months’ follow-up. In conclusion, NfL plasma levels are elevated during ECM confirming brain damage. However, NfL plasma levels fail short on reliably indicating on the final outcomes in the acute disease stage that could be either fatal or reversible. Increased levels of plasma NfL during the acute disease stage are thus likely driven by the anatomical location of brain damage, the olfactory bulb, a region that serves as cerebral draining pathway into the nasal lymphatics.
Objectives
Magnetic resonance imaging (MRI) image quality can be severely impaired by artifacts caused by fixed orthodontic retainers. In clinical practice, there is a trend towards using ...computer-aided design/computer-aided manufacturing (CAD/CAM) retainers. This study aimed to quantify MRI artifacts produced by these novel CAD/CAM retainers.
Material and methods
Three CAD/CAM retainers and a stainless-steel retainer (“Twistflex”; clinical reference standard) were scanned in vitro at 3-T MRI using a high-resolution 3D sequence. The artifact diameters and three-dimensional artifact volumes (AV) were determined for all mandibular (AV
mand
) and maxillary (AV
max
) retainers. Moreover, the corresponding ratio of artifact volume to retainer volume (AV/RV
mand
, AV/RV
max
) was calculated.
Results
Twistflex caused large artifact volumes (AV
mand
: 13530 mm
3
; AV
max
: 15642 mm
3
; AV/RV
mand
: 2602; AV/RV
max
: 2235). By contrast, artifact volumes for CAD/CAM retainers were substantially smaller: whereas artifact volumes for cobalt–chromium retainers were moderate (381 mm
3
; 394 mm
3
; 39; 31), grade-5 titanium (110 mm
3
; 126 mm
3
; 12; 12) and nickel–titanium (54 mm
3
; 78 mm
3
; 12; 14) both produced very small artifact volumes.
Conclusion
All CAD/CAM retainers caused substantially smaller volumes of MRI artifacts compared to Twistflex. Grade-5 titanium and nickel–titanium CAD/CAM retainers showed the smallest artifact volumes.
Clinical relevance
CAD/CAM retainers made from titanium or nickel–titanium may not relevantly impair image quality in head/neck and dental MRI. Artifacts caused by cobalt–chromium CAD/CAM retainers may mask nearby dental/periodontal structures. In contrast, the large artifacts caused by Twistflex are likely to severely impair diagnosis of oral and adjacent pathologies.
To apply the MB (multiband) excitation and blipped-CAIPI (blipped-controlled aliasing in parallel imaging) techniques in a spin and gradient-echo (SAGE) EPI sequence to improve the slice coverage for ...vessel architecture imaging (VAI).
Both MB excitation and blipped-CAIPI with in-plane parallel imaging were incorporated into a gradient-echo (GE)/spin-echo (SE) EPI sequence for simultaneous tracking of the dynamic MR signal changes in both GE and SE contrasts after the injection of contrast agent. MB and singleband (SB) excitation were compared using a 20-channel head coil at 3 Tesla, and high-resolution MB VAI could be performed in 32 glioma patients.
Whole-brain covered high resolution VAI can be achieved after applying multiband excitation with a factor of 2 and in-plane parallel imaging with a factor of 3. The quality of the images resulting from MB acceleration was comparable to those from the SB method: images were reconstructed without any loss of spatial resolution or severe distortions. In addition, MB and SB signal-to-noise ratios (SNR) were similar. A relative low g-factor induced from the MB acceleration method was achieved after using a blipped-CAIPI technique (1.35 for GE and 1.33 for SE imaging). Performing quantitative VAI, we found that, among all VAI parametric maps, microvessel type indicator (MTI), distance map (I) and vascular-induced bolus peak-time shift (VIPS) were highly correlated. Likewise, VAI parametric maps of slope, slope length and short axis were highly correlated.
Multiband accelerated SAGE successfully doubles the number of readout slices in the same measurement time when compared to conventional readout sequences. The corresponding VAI parametric maps provide insights into the complexity and heterogeneity of vascular changes in glioma.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The treatment of vasospasms during endovascular stroke treatment (EST) with intra-arterial nimodipine (NM) is routinely performed. However, the efficacy of resolving iatrogenic vasospasms during the ...angiographic intervention and the infarct development in follow-up imaging after EST has not been studied yet.
Retrospective single-center analysis of patients receiving EST for anterior circulation vessel occlusion between 01/2015 and 12/2021. The primary endpoint was ASPECTS in follow-up imaging. Secondary endpoints were the clinical outcome (combined endpoint NIHSS 24 h after EST and difference between modified Rankin Scale (mRS) before stroke and at discharge (delta mRS)) and intracranial hemorrhage (ICH) in follow-up imaging. Patients with vasospasms receiving NM (NM+) or not (NM-) were compared in univariate analysis.
Vasospasms occurred in 79/1283 patients (6.2%), who consecutively received intra-arterial NM during EST. The targeted vasospasm angiographically resolved in 84% (66/79) under NM therapy. ASPECTS was lower in follow-up imaging after vasospasms and NM-treatment (NM - 7 (6-9), NM + 6 (4.5-8), p = 0.013) and the clinical outcome was worse (NIHSS 24 h after EST was higher in patients treated with NM (median, IQR; NM+: 14, 5-21 vs. NM-: 9, 3-18; p = 0.004), delta-mRS was higher in the NM + group (median, IQR; NM+: 3, 1-4 vs. NM-: 2, 1-2; p = 0.011)). Any ICH (NM+: 27/79, 34.2% vs. NM-: 356/1204, 29.6%; p = 0.386) and symptomatic ICH (NM+: 2/79, 2.5% vs. NM-: 21/1204, 1.7%; p = 0.609) was equally distributed between groups.
Intra-arterial nimodipine during EST resolves iatrogenic vasospasms efficiently during EST without increasing intracranial hemorrhage rates. However, patients with vasospasms and NM treatment show higher infarct growth resulting in lower ASPECTS in follow-up imaging.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cerebral organoids recapitulate the structure and function of the developing human brain in vitro, offering a large potential for personalized therapeutic strategies. The enormous growth of this ...research area over the past decade with its capability for clinical translation makes a non-invasive, automated analysis pipeline of organoids highly desirable. This work presents a novel non-invasive approach to monitor and analyze cerebral organoids over time using high-field magnetic resonance imaging and state-of-the-art tools for automated image analysis. Three specific objectives are addressed, (I) organoid segmentation to investigate organoid development over time, (II) global cysticity classification and (III) local cyst segmentation for organoid quality assessment. We show that organoid growth can be monitored reliably over time and cystic and non-cystic organoids can be separated with high accuracy, with on par or better performance compared to state-of-the-art tools applied to brightfield imaging. Local cyst segmentation is feasible but could be further improved in the future. Overall, these results highlight the potential of the pipeline for clinical application to larger-scale comparative organoid analysis.
It is poorly understood how progressive brain swelling in experimental cerebral malaria (ECM) evolves in space and over time, and whether mechanisms of inflammation or microvascular ...sequestration/obstruction dominate the underlying pathophysiology. We therefore monitored in the Plasmodium berghei ANKA-C57BL/6 murine ECM model, disease manifestation and progression clinically, assessed by the Rapid-Murine-Coma-and-Behavioral-Scale (RMCBS), and by high-resolution in vivo MRI, including sensitive assessment of early blood-brain-barrier-disruption (BBBD), brain edema and microvascular pathology. For histological correlation HE and immunohistochemical staining for microglia and neuroblasts were obtained. Our results demonstrate that BBBD and edema initiated in the olfactory bulb (OB) and spread along the rostral-migratory-stream (RMS) to the subventricular zone of the lateral ventricles, the dorsal-migratory-stream (DMS), and finally to the external capsule (EC) and brainstem (BS). Before clinical symptoms (mean RMCBS = 18.5±1) became evident, a slight, non-significant increase of quantitative T2 and ADC values was observed in OB+RMS. With clinical manifestation (mean RMCBS = 14.2±0.4), T2 and ADC values significantly increased along the OB+RMS (p = 0.049/p = 0.01). Severe ECM (mean RMCBS = 5±2.9) was defined by further spread into more posterior and deeper brain structures until reaching the BS (significant T2 elevation in DMS+EC+BS (p = 0.034)). Quantitative automated histological analyses confirmed microglial activation in areas of BBBD and edema. Activated microglia were closely associated with the RMS and neuroblasts within the RMS were severely misaligned with respect to their physiological linear migration pattern. Microvascular pathology and ischemic brain injury occurred only secondarily, after vasogenic edema formation and were both associated less with clinical severity and the temporal course of ECM. Altogether, we identified a distinct spatiotemporal pattern of microglial activation in ECM involving primarily the OB+RMS axis, a distinct pathway utilized by neuroblasts and immune cells. Our data suggest significant crosstalk between these two cell populations to be operative in deeper brain infiltration and further imply that the manifestation and progression of cerebral malaria may depend on brain areas otherwise serving neurogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Little is known about the value of high‐resolution follow‐up imaging in patients with neuralgic amyotrophy (NA) and the question of the best treatment algorithm remains unclear. Three patients (one ...female, two male) with the clinical presentation of SARS‐CoV‐2‐vaccination‐associated NA underwent initial magnetic resonance neurography (MRN) imaging and follow‐up examinations. All patients showed a marked clinical improvement, independent of treatment, including an almost full recovery of motor function over the course of 8–12 months which was accurately mirrored by imaging findings on MRN. MRN imaging is a valuable tool for monitoring the further clinical course of patients suffering from vaccination‐associated NA.
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