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.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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 (R2 0.95-0.96) and SPACE (R2 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.
- Publikační typ
- časopisecké články MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Gadolinium retention in various organs including the brain after application of MR contrast agents is a important phenomenon. Its pathophysiology and clinical relevance have not yet been reliably evaluated. Gadolinium retention in the brain may be monitored by measuring T1 and T2 relaxation times in regions with high ferritin concentration due to gadolinium binding. The prospective study aims, by means of repeated quantitative MR examinations after clinically-indicated contrast application, to better understand this phenomenon. A pilot study showed that after an initial shortening of T1 and T2 relaxation times in the globus pallidus after repeated applications of MR contrast agents, a certain plateau is reached or relaxation times are prolonged. This phenomenon has not yet been reliably evaluated. By means of repeated non-contrast enhanced quantitative measurements in a group of approximately 100 patients we aim to study this phenomenon more thoroughly. A comparative group of healthy volunteers will also be studied, however contrast agents will not be applied.
Retence gadolinia po aplikaci MR kontrastních látek v různých orgánech včetně mozku je nedávno objeveným a závažným fenoménem, jehož patofyziologie a klinická relevance nebyly dosud spolehlivě popsány. Retenci gadolinia lze v mozku neinvazivne monitorovat pomocí alterace T1 a T2 relaxačních časů v oblastech s vysokou koncentrací ferritinu, na který se gadolinium váže. Prospektivní studie má za cíl opakovanými kvantitativními MR vyšetřeními, po předchozí aplikaci MR kontrastní látky z klinické indikace, lépe objasnit tento závažný fenomén. Pilotní studie ukazují, že po počátečním zkrácení T1 a T2 relaxačních časů v globus pallidus po aplikaci MR kontrastních látek, dochází k určitému plateau, případně i k jejich prodloužení. Tento fenomén nebyl dosud spolehlivě popsán. Opakovanými nekontrastnmí kvantitativními měřeními u skupiny cca 100 pacientů hodláme tento fenomén podrobně studovat. Srovnatelná skupina zdravých dobrovolníků pak bude obdobně sledována pomocí kvantitativní MR, bez aplikace kontrastní látky.
- Klíčová slova
- magnetická rezonance, Magnetic resonance, kontrastní látka, retence gadolinia, globus pallidus, nucleus dentatus, contrast agent, gadolinium retention, globus pallidus, dentate nucleus,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Primary progressive aphasias (PPA) are neurodegenerative disorders with an initial isolated language impairment progressing into dementia. Data about individual progression of PPA patients are sparse, as most large studies are retrospective. The project is designed as a prospective longitudinal multicenter cohort study. We emphasize to include 50-60 PPA patients, as comparative cohorts 20-30 patients with frontotemporal dementia, 20-30 Alzheimer’s disease patients and 20-30 patients with vascular aphasia. We already dispose of data from 50 mild cognitive impairment subjects, 50 Parkinson disease subjects and 50 healthy controls. All patients will be examined using neuropsychological tests, MRI, biomarkers of neurodegeneration; and in selected patients, neuropathological examination will be done. Expected outcomes include improvement of early diagnosis of PPA, composition of an appropriate neuropsychological battery for early assessment of PPA subtypes and their linguistic analysis and better prognostic estimates in PPA.
Primární progresivní afázie (PPA) jsou neurodegenerativní onemocnění, která se vyznačují izolovanou alterací řeči s postupnou progresí do demence. Je jen málo údajů o individuální progresi pacientů s PPA a větší publikované studie jsou retrospektivní. Navrhovaný projekt je koncipován jako longitudinální multicentrická kohortová studie. Předpokládáme vyšetření 50-60 pacientů s PPA. Srovnávacím souborem bude 20-30 pacientů s frontotemporální demencí, 20-30 pacientů s Alzheimerovu nemocí, a 20-30 pacientů s vaskulární afázií. V současné době již disponujeme daty od 50 pacientů s mírnou kognitivní poruchou, 50 pacientů s Parkinsonovou nemocí a 50 zdravých dobrovolníků. Pacienti budou vyšetřováni neuropsychologickými testy, MRI, budou stanovovány biomarkery neurodegenerací a ve vybraných případech i neuropatologické vyšetření. Výstupem bude zlepšení časné diagnózy PPA, vytvoření baterie neuropsychologických testů pro včasnou diagnózu, lingvistická analýz subtypů PPA a zpřesnění prognostického očekávání u pacientů s PPA.
- Klíčová slova
- magnetická rezonance, magnetic resonance imaging, demence, dementia, neurodegeneration, Alzheimer's disease, Alzheimerova nemoc, progresivní afázie, neurodegenerace, frontotemporální demence, afázie, primary progressive aphasia, frontotemporal dementia, aphasia,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
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.
In functional magnetic imaging (fMRI) in Parkinson's disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients' tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structure's temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients' finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loop's structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n = 31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.
- Publikační typ
- abstrakt z konference MeSH
INTRODUCTION: Esophageal achalasia is a primary motility disorder. Although the exact pathogenesis is unknown, autoimmune, and neurodegenerative processes seem to be involved similarly to neurodegenerative and/or demyelinating disorders (NDDs). We hypothesized that the prevalence of NDD may be higher among patients with achalasia and vice versa as the background pathogenetic mechanisms are similar. METHODS: This was a prospective, comparative questionnaire-based study. Patients with achalasia and patients with NDD were enrolled. Selected patients with achalasia were thoroughly examined by a neurologist and selected patients with NDD were examined by a gastroenterologist to confirm or rule out NDD or achalasia. We assessed the prevalence of both achalasia and NDD and compared them with their prevalence in general population. RESULTS: A total of 150 patients with achalasia and 112 patients with NDD were enrolled. We observed an increased prevalence of NDD among patients with achalasia (6.0% (9/150); 95% CI (confidence interval): 3.1-11.2%) as compared to the estimated 2.0% prevalence in general population (p = 0.003). Although 32 out of 112 patients (28.6%) with NDD reported dysphagia, we did not observe significantly increased prevalence of achalasia in these patients (1.8% (2/112) vs 0.8% in general population, p = 0.226). CONCLUSION: The prevalence of NDD was significantly higher among patients with achalasia (6.0%) compared to general population (2.0%), suggesting an association of these disorders. Large-volume studies are necessary to confirm this finding.
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: 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. RESULTS: 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. DISCUSSION: 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.
- Publikační typ
- časopisecké články MeSH
