Gadolinium-based contrast agents (GBCA) were introduced with high expectations for favorable efficacy, low nephrotoxicity, and minimal allergic-like reactions. Nephrogenic systemic fibrosis and ...proven gadolinium retention in the body including the brain has led to the restriction of linear GBCAs and a more prudent approach regarding GBCA indication and dosing. In this review, we present the chemical, physical, and clinical aspects of this topic and aim to provide an equanimous and comprehensive summary of contemporary knowledge with a perspective of the future. In the first part of the review, we present various elements and compounds that may serve as MRI contrast agents. Several GBCAs are further discussed with consideration of their relaxivity, chelate structure, and stability. Gadolinium retention in the brain is explored including correlation with the presence of metalloprotein ferritin in the same regions where visible hyperintensity on unenhanced T1-weighted imaging occurs. Proven interaction between ferritin and gadolinium released from GBCAs is introduced and discussed, as well as the interaction of other elements with ferritin; and manganese in patients with impaired liver function or calcium in Fahr disease. We further present the concept that only high-molecular-weight forms of gadolinium can likely visibly change signal intensity on unenhanced T1-weighted imaging. Clinical data are also presented with respect to potential neurological manifestations originating from the deep-brain nuclei. Finally, new contrast agents with relatively high relaxivity and stability are introduced.
Critical relevance statement
GBCA may accumulate in the brain, especially in ferritin-rich areas; however, no adverse neurological manifestations have been detected in relation to gadolinium retention.
Key Points
Gadolinium currently serves as the basis for MRI contrast agents used clinically.
No adverse neurological manifestations have been detected in relation to gadolinium retention.
Future contrast agents must advance chelate stability and relativity, facilitating lower doses.
Graphical Abstract
Purpose
Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015 based on the randomized ...controlled EF-14 study. Subsequent approvals worldwide and increased adoption over time have raised the question of whether a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role.
Methods
We conducted a literature search to identify clinical studies evaluating overall survival (OS) in TTFields-treated patients. Comparative and single-cohort studies were analyzed. Survival curves were pooled using a distribution-free random-effects method.
Results
Among nine studies, seven (N = 1430 patients) compared the addition of TTFields therapy to standard of care (SOC) chemoradiotherapy versus SOC alone and were included in a pooled analysis for OS. Meta-analysis of comparative studies indicated a significant improvement in OS for patients receiving TTFields and SOC versus SOC alone (HR: 0.63; 95% CI 0.53–0.75;
p
< 0.001). Among real-world post-approval studies, the pooled median OS was 22.6 months (95% CI 17.6–41.2) for TTFields-treated patients, and 17.4 months (95% CI 14.4–21.6) for those not receiving TTFields. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields use. Furthermore, for patients included in studies reporting data on device usage (N = 1015), an average usage rate of ≥ 75% was consistently associated with prolonged survival (
p
< 0.001).
Conclusions
Meta-analysis of comparative TTFields studies suggests survival may be improved with the addition of TTFields to SOC for patients with newly diagnosed GBM.
The prognosis of glioblastoma remains unfavorable. TTFields utilize low intensity electric fields (frequency 150-300 kHz) that disrupt cellular processes critical for cancer cell viability and tumor ...progression. TTFields are delivered via transducer arrays placed on the patients' scalp. Methods: Between the years 2004 and 2022, 55 patients (20 female), aged 21.9-77.8 years (mean age 47.3±11.8 years; median 47.6 years) were treated with TTFields for newly-diagnosed GBM, and compared to 54 control patients (20 females), aged 27.0-76.7 years (mean age 51.4±12.2 years; median 51.7 years) (p=0.08). All patients underwent gross total or partial resection of GBM. One patient had biopsy only. When available, MGMT promoter methylation status and IDH mutation was detected.
Patients on TTFields therapy demonstrated improvements in PFS and OS relative to controls (hazard ratio: 0.64, p=0.031; and 0.61, p=0.028 respectively). TTFields average time on therapy was 74.8% (median 82%): median PFS of these patients was 19.75 months. Seven patients with TTFields usage ≤60% (23-60%, mean 46.3%, median 53%) had a median PFS of 7.95 months (p=0.0356). Control patients with no TTFields exposure had a median PFS of 12.45 months. Median OS of TTF patients was 31.67 months compared to 24.80 months for controls.
This is the most extensive study on newly-diagnosed GBM patients treated with TTFields, covering a period of 18 years at a single center and presenting not only data from clinical trials but also a group of 36 patients treated with TTFields as a part of routine clinical practice.
Objectives
Accurate detection of metastatic brain lesions (MBL) is critical due to advances in radiosurgery. We compared the results of three readers in detecting MBL using T1-weighted 2D spin echo ...(SE) and sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences with whole-brain coverage at both 1.5 T and 3 T.
Methods
Fifty-six patients evaluated for MBL were included and underwent a standard protocol (1.5 T,
n
= 37; 3 T,
n
= 19), including postcontrast T1-weighted SE and SPACE. The rating was performed by three raters in two sessions > six weeks apart. The true number of MBL was determined using all available imaging including follow-up. Intraclass correlations for intra-rater and inter-rater agreement were calculated. Signal intensity ratios (SIR; enhancing lesion, white matter) were determined on a subset of 46 MBL > 4 mm. A paired
t
-test was used to evaluate postcontrast sequence order and SIR. Reader accuracy was evaluated by the coefficient of determination.
Results
A total of 135 MBL were identified (mean/subject 2.41, SD 6.4). The intra-rater agreement was excellent for all 3 raters (ICC = 0.97–0.992), as was the inter-rater agreement (ICC = 0.995 SE, 0.99 SPACE). Subjective qualitative ratings were lower for SE images; however, signal intensity ratios were higher in SE sequences. Accuracy was high in all readers for both SE (
R
2
0.95–0.96) and SPACE (
R
2
0.91–0.96) sequences.
Conclusions
Although SE sequences are superior to gradient echo sequences in the detection of small MBL, they have long acquisition times and frequent artifacts. We show that T1-weighted SPACE is not inferior to standard thin-slice SE sequences in the detection of MBL at both imaging fields.
Critical relevance statement
Our results show the suitability of 3D T1-weighted turbo spin echo (TSE) sequences (SPACE, CUBE, VISTA) in the detection of brain metastases at both 1.5 T and 3 T.
Key points
• Accurate detection of brain metastases is critical due to advances in radiosurgery.
• T1-weighted SE sequences are superior to gradient echo in detecting small metastases.
• T1-weighted 3D-TSE sequences may achieve high resolution and relative insensitivity to artifacts.
• T1-weighted 3D-TSE sequences have been recommended in imaging brain metastases at 3 T.
• We found T1-weighted 3D-TSE equivalent to thin-slice SE at 1.5 T and 3 T.
Graphical Abstract
Huntington's disease (HD) is an inherited neurodegenerative disorder with progressive impairment of motor, behavioral and cognitive functions. The clinical features of HD are closely related to the ...degeneration of the basal ganglia, predominantly the striatum. The main striatal output structure, the globus pallidus, strongly accumulates metalloprotein-bound iron, which was recently shown to influence the diffusion tensor scalar values. To test the hypothesis that this effect dominates in the iron-rich basal ganglia of HD patients, we examined the globus pallidus using DTI and T2 relaxometry sequences. Quantitative magnetic resonance (MR), clinical and genetic data (number of CAG repeats) were obtained from 14 HD patients. MR parameters such as the T2 relaxation rate (RR), fractional anisotropy (FA) and mean diffusivity (MD) were analysed. A positive correlation was found between RR and FA (R2=0.84), between CAG and RR (R2=0.59) and between CAG and FA (R2=0.44). A negative correlation was observed between RR and MD (R2=0.66). A trend towards correlation between CAG and MD was noted. No correlation between MR and clinical parameters was found. Our results indicate that especially magnetic resonance FA measurements in the globus pallidus of HD patients may be strongly affected by metalloprotein-bound iron accumulation.
Background
Cerebrovascular disease represents a major source of global mortality and morbidity. Imaging examinations play a critical role in the management of stroke patients, from establishing the ...initial diagnosis to determining and guiding further treatment.
Methods
In this article, current CT and MRI methods employed in the management of stroke patients are reviewed, with an emphasis on ischemic stroke.
Results
The advantages and disadvantages of these techniques are discussed, a number of cases emphasizing key points are presented, and a comparison between modern CT and MRI techniques is outlined.
Conclusion
The major drawback of CT is the high radiation dose, while in MRI it is the more complicated and time-consuming aspect of the examination.
Main Messages
•
Cerebrovascular disease represents a major source of global mortality and morbidity
•
Imaging examinations play a critical role in the management of stroke patients
•
The penumbra may be seen with both CT and MRI; however, this concept may be overly simplistic
•
The major drawback of CT is the high radiation dose, while MRI is a more complicated examination
Fractional anisotropy (FA) is the most commonly used quantitative measure of diffusion in the brain. Changes in FA have been reported in many neurological disorders, but the implementation of ...diffusion tensor imaging (DTI) in daily clinical practice remains challenging. We propose a novel color look-up table (LUT) based on normative data as a tool for screening FA changes. FA was calculated for 76 healthy volunteers using 12 motion-probing gradient directions (MPG), a subset of 59 subjects was additionally scanned using 30 MPG. Population means and 95% prediction intervals for FA in the corpus callosum, frontal gray matter, thalamus and basal ganglia were used to create the LUT. Unique colors were assigned to inflection points with continuous ramps between them. Clinical use was demonstrated on 17 multiple system atrophy (MSA) patients compared to 13 patients with Parkinson disease (PD) and 17 healthy subjects. Four blinded radiologists classified subjects as MSA/non-MSA. Using only the LUT, high sensitivity (80%) and specificity (84%) were achieved in differentiating MSA subjects from PD subjects and controls. The LUTs generated from 12 and 30 MPG were comparable and accentuate FA abnormalities.
Gadolinium deposition in the brain following administration of gadolinium-based contrast agents (GBCAs) has led to health concerns. We show that some clinical GBCAs form Gd
3+
-ferritin nanoparticles ...at (sub)nanomolar concentrations of Gd
3+
under physiological conditions. We describe their structure at atomic resolution and discuss potential relevance for clinical MRI.
We show that clinical gadolinium-based contrast agents can form Gd
3+
-ferritin nanoparticles under physiological conditions. We suggest they can contribute to the T
1
intensity changes in ferritin-rich brain areas observed in patients examined by MRI.
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