This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS ...imaging.
Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols.
Purpose
As the field of CEST grows, various novel preparation periods using different parameters are being introduced. At the same time, large, multisite clinical studies require clearly defined ...protocols, especially across different vendors. Here, we propose a CEST definition standard using the open Pulseq format for a shareable, simple, and exact definition of CEST protocols.
Methods
We present the benefits of such a standard in three ways: (1) an open database on GitHub, where fully defined, human‐readable CEST protocols can be shared; (2) an open‐source Bloch‐McConnell simulation to test and optimize CEST preparation periods in silico; and (3) a hybrid MR sequence that plays out the CEST preparation period and can be combined with any existing readout module.
Results
The exact definition of the CEST preparation period, in combination with the flexible simulation, leads to a good match between simulations and measurements. The standard allowed finding consensus on three amide proton transfer–weighted protocols that could be compared in healthy subjects and a tumor patient. In addition, we could show coherent multisite results for a sophisticated CEST method, highlighting the benefits regarding protocol sharing and reproducibility.
Conclusion
With Pulseq‐CEST, we provide a straightforward approach to standardize, share, simulate, and measure different CEST preparation schemes, which are inherently completely defined.
The prognosis of spontaneous intracerebral hemorrhage (sICH) is poor because of the mass effect arising from the hematoma and the associated peri-hemorrhagic edema, leading to increased intracranial ...pressure. Because the efficacy of surgical and anti-edematous treatment strategies is limited, we investigated the effects of mild induced hypothermia in patients with large sICH.
Twelve patients with supratentorial sICH >25 mL were treated by hypothermia of 35 degrees C for 10 days. Evolution of hematoma volume and perifocal edema was measured by cranial CT. Functional outcome was assessed after 90 days. These patients were compared to patients (n=25; inclusion criteria: sICH volume >25 mL, no acute restriction of medical therapy on admission) from the local hemorrhage data bank (n=312). Side effects of hypothermia were analyzed.
All patients from both groups needed mechanical ventilation and were treated in a neurocritical care unit. All hypothermic patients (mean age, 60+/-10 years) survived until day 90, whereas 7 patients died in the control group (mean age, 67+/-7 years). Absolute hematoma size on admission was 58+/-29 mL (hypothermia) compared to 57+/-31 mL (control). In the hypothermia group, edema volume remained stable during 14 days (day 1, 53+/-43 mL; day 14, 57+/-45 mL), whereas edema significantly increased in the control group from 40+/-28 mL (day 1) to 88+/-47 mL (day 14). ICH continuously dissolved in both groups. Pneumonia rate was 100% in the hypothermia group and 76% in controls (P=0.08). No significant side effects of hypothermia were observed.
Hypothermia prevented the increase of peri-hemorrhagic edema in patients with large sICH.
Abstract To treat tumours efficiently and spare normal tissues, targeted drug delivery is a promising alternative to conventional, systemic administered chemotherapy. Drug-carrying magnetic ...nanoparticles can be concentrated in tumours by external magnetic fields, preventing the nanomaterial from being cleared by metabolic burden before reaching the tumour. Therefore in Magnetic Drug Targeting (MDT) the favoured mode of application is believed to be intra-arterial. Here, we show that a simple yet versatile magnetic carrier-system (hydrodynamic particles diameter < 200 nm) accumulates the chemotherapeutic drug mitoxantrone efficiently in tumours. With MDT we observed the following drug accumulations relative to the recovery from all investigated tissues: tumour region: 57.2%, liver: 14.4%, kidneys: 15.2%. Systemic intra-venous application revealed different results: tumour region: 0.7%, liver: 14.4 % and kidneys: 77.8%. The therapeutic outcome was demonstrated by complete tumour remissions and a survival probability of 26.7% ( P = 0.0075). These results are confirming former pilot experiments and implying a milestone towards clinical studies. From the Clinical Editor This team of investigators studied drug carrying nanoparticles for magnetic drug targeting (MDT), demonstrating the importance of intra-arterial administration resulting in improved clinical outcomes in the studied animal model compared with intra-venous.
Visual art represents a powerful resource for mental and physical well-being. However, little is known about the underlying effects at a neural level. A critical question is whether visual art ...production and cognitive art evaluation may have different effects on the functional interplay of the brain's default mode network (DMN). We used fMRI to investigate the DMN of a non-clinical sample of 28 post-retirement adults (63.71 years ±3.52 SD) before (T0) and after (T1) weekly participation in two different 10-week-long art interventions. Participants were randomly assigned to groups stratified by gender and age. In the visual art production group 14 participants actively produced art in an art class. In the cognitive art evaluation group 14 participants cognitively evaluated artwork at a museum. The DMN of both groups was identified by using a seed voxel correlation analysis (SCA) in the posterior cingulated cortex (PCC/preCUN). An analysis of covariance (ANCOVA) was employed to relate fMRI data to psychological resilience which was measured with the brief German counterpart of the Resilience Scale (RS-11). We observed that the visual art production group showed greater spatial improvement in functional connectivity of PCC/preCUN to the frontal and parietal cortices from T0 to T1 than the cognitive art evaluation group. Moreover, the functional connectivity in the visual art production group was related to psychological resilience (i.e., stress resistance) at T1. Our findings are the first to demonstrate the neural effects of visual art production on psychological resilience in adulthood.
Fundamental processes influencing human growth can be revealed by studying extreme short stature. Using genetic linkage analysis, we find that biallelic loss-of-function mutations in the centrosomal ...pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II) in 25 patients. Adults with this rare inherited condition have an average height of 100 centimeters and a brain size comparable to that of a 3-month-old baby, but are of near-normal intelligence. Absence of PCNT results in disorganized mitotic spindles and missegregation of chromosomes. Mutations in related genes are known to cause primary microcephaly (MCPH1, CDK5RAP2, ASPM, and CENPJ).
There is evidence that glaucoma is a neurodegenerative disease involving the whole visual pathway. We prospectively examined potential benefits of volumetry of the lateral geniculate nucleus (LGN) ...and diffusion tensor imaging (DTI) using a new 7T scanner.
20 patients with normal tension glaucoma and 16 control individuals were examined. LGN volume and fractional anisotropy (FA) of the optic tract (OT) and the optic radiation (OR) and their correlation with RNFL (retinal nerve fiber layer) thickness were analyzed.
LGN volume was significantly reduced in NTG (60.9 vs 88.3; p < 0.05). FA of the OT (right: 0.35 vs 0.66, left: 0.36 vs 0.67; p < 0.05) and of the OR (right: 0.41 vs 0.70, left: 0.41 vs 0.69; p < 0.05) was also significantly reduced. Nasal RNFL thickness correlated with the volume of the contralateral LGN (r = 0.471, p = 0.05). Temporal RNFL thickness correlated with the volume of the ipsilateral LGN (r = 0.603, p = 0.015).
NTG leads to significant atrophy of the LGN compared to controls. FA of the optic tract and the optic radiation is reduced in NTG as sign of axonal degeneration. RNFL thickness but not FA correlates with LGN volume.
The glutamate transporter xCT (SCL7a11, system Xc-, SXC) is an emerging key player in glutamate/cysteine/glutathione homeostasis in the brain and in cancer. xCT expression correlates with the grade ...of malignancy. Here, we report on the use of the U.S. Food and Drug Administration and EMA-approved xCT inhibitor, sulfasalazine (SAS) in gliomas. SAS does not affect cell viability in gliomas at concentrations below 200 µM. At higher concentrations SAS becomes gliomatoxic. Mechanistically SAS inhibits xCT and induces ferroptotic cell death in glioma cells. There is no evidence for impact on autophagic flux following SAS application. However, SAS can potentiate the efficacy of the standard chemotherapeutic and autophagy-inducing agent temozolomide (Temcat, Temodal or Temodar®). We also investigated SAS in non-transformed cellular constituents of the brain. Neurons and brain tissue are almost non-responding to SAS whereas isolated astrocytes are less sensitive towards SAS toxicity compared to gliomas. In vivo SAS treatment does not affect experimental tumor growth and treated animals revealed comparable tumor volume as untreated controls. However, SAS treatment resulted in reduced glioma-derived edema and, hence, total tumor volume burden as revealed by T2-weighted magnetic resonance imaging. Altogether, we show that SAS can be utilized for targeting the glutamate antiporter xCT activity as a tumor microenvironment-normalizing drug, while crucial cytotoxic effects in brain tumors are minor.
Radiotherapy (RT) is commonly applied for the treatment of glioblastoma multiforme (GBM). Following the planning target volume (PTV) definition procedure standardized in guidelines, a 20% risk of ...missing non-local recurrences is present. Purpose of this study was to evaluate whether diffusion tensor imaging (DTI)-based fiber tracking may be beneficial for PTV definition taking into account the prediction of distant recurrences. 56 GBM patients were examined with magnetic resonance imaging (MRI) including DTI performed before RT after resection of the primary tumor. Follow-up MRIs were acquired in three month intervals. For the seven patients with a distant recurrence, fiber tracking was performed with three algorithms and it was evaluated whether connections existed from the primary tumor region to the distant recurrence. It depended strongly on the used tracking algorithm and the used tracking parameters whether a connection was observed. Most of the connections were weak and thus not usable for PTV definition. Only in one of the seven patients with a recurring tumor, a clear connection was present. It seems unlikely that DTI-based fiber tracking can be beneficial for predicting distant recurrences in the planning of PTVs for glioblastoma multiforme.
Acute ischemic stroke (AIS) is a leading global cause of mortality and morbidity. Improving long-term outcome predictions after thrombectomy can enhance treatment quality by supporting clinical ...decision-making. With the advent of interpretable deep learning methods in recent years, it is now possible to develop trustworthy, high-performing prediction models. This study introduces an uncertainty-aware, graph deep learning model that predicts endovascular thrombectomy outcomes using clinical features and imaging biomarkers. The model targets long-term functional outcomes, defined by the three-month modified Rankin Score (mRS), and mortality rates. A sample of 220 AIS patients in the anterior circulation who underwent endovascular thrombectomy (EVT) was included, with 81 (37%) demonstrating good outcomes (mRS
2). The performance of the different algorithms evaluated was comparable, with the maximum validation under the curve (AUC) reaching 0.87 using graph convolutional networks (GCN) for mRS prediction and 0.86 using fully connected networks (FCN) for mortality prediction. Moderate performance was obtained at admission (AUC of 0.76 using GCN), which improved to 0.84 post-thrombectomy and to 0.89 a day after stroke. Reliable uncertainty prediction of the model could be demonstrated.
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