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
We have recently shown that low intensity, intermediate frequency, electric fields inhibit by an anti-microtubule mechanism of action, cancerous cell growth in vitro. Using implanted electrodes, ...these fields were also shown to inhibit the growth of dermal tumors in mice. The present study extends these findings to additional cell lines human breast carcinoma; MDA-MB-231, and human non-small-cell lung carcinoma (H1299) and to animal tumor models (intradermal B16F1 melanoma and intracranial F-98 glioma) using external insulated electrodes. These findings led to the initiation of a pilot clinical trial of the effects of TTFields in 10 patients with recurrent glioblastoma (GBM). Median time to disease progression in these patients was 26.1 weeks and median overall survival was 62.2 weeks. These time to disease progression and OS values are more than double the reported medians of historical control patients. No device-related serious adverse events were seen after >70 months of cumulative treatment in all of the patients. The only device-related side effect seen was a mild to moderate contact dermatitis beneath the field delivering electrodes. We conclude that TTFields are a safe and effective new treatment modality which effectively slows down tumor growth in vitro, in vivo and, as demonstrated here, in human cancer patients.
•Emotional matching in PD was impaired and restored with dopaminergic medication.•PD patients showed increased BOLD response to emotion in the visual cortex.•BOLD differences between PD and controls ...were not dependent on cognitive function.•Cognitive impairment in PD was associated with deficits for non-emotional stimuli.•Findings suggest independent emotional and cognitive impairments in PD.
Emotional and cognitive impairments in Parkinson's disease (PD) are prevalent, hamper interpersonal relations and reduce quality of life. It is however unclear to what extent these domains interplay in PD-related deficits and how they are influenced by dopaminergic availability. This study examined the effect of cognitive impairment and dopaminergic medication on neural and behavioral mechanisms of facial emotion recognition in PD patients. PD patients on and off dopaminergic medication and matched healthy controls underwent an emotional face matching task during functional MRI. In addition, a comprehensive neuropsychological evaluation of cognitive function was conducted. Increased BOLD response to emotional faces was found in the visual cortex of PD patients relative to controls irrespective of cognitive function and medication status. Administration of dopaminergic medication in PD patients resulted in restored behavioral accuracy for emotional faces relative to controls and decreased retrosplenial cortex BOLD response to emotion relative to off-medication state. Furthermore, cognitive impairment in PD patients was associated with reduced behavioral accuracy for non-emotional stimuli and predicted BOLD response to emotion in the anterior and posterior cingulate cortices, depending on medication status. Findings of aberrant visual and retrosplenial BOLD response to emotion are suggested to stem from altered attentional and/or emotion-driven modulation from subcortical and higher cortical regions. Our results indicate neural disruptions and behavioral deficits in emotion processing in PD patients that are dependent on dopaminergic availability and independent of cognitive function. Our findings highlight the importance of dopaminergic treatment not only for the motor symptoms but also the emotional disturbances in PD.
Magnetic resonance imaging (MRI) of pacemaker patients is contraindicated due to documented potential risks to the patient from hazardous interactions between the MRI and pacemaker system.
The ...purpose of this prospective, randomized, controlled, worldwide clinical trial was to evaluate the safety and effectiveness of a pacemaker system designed for safe use in MRI for any bradycardia indicated patient.
Patients (n = 464) were randomized to undergo an MRI scan between 9 and 12 weeks postimplant (MRI group, n = 258) or not to undergo MRI (control group, n = 206) after successful implantation of the specially designed dual-chamber pacemaker and leads. Patients were monitored for arrhythmias, symptoms, and pacemaker system function during 14 nonclinically indicated relevant brain and lumbar MRI sequences. Sequences were performed at 1.5 T and included scans with high radiofrequency power deposition and/or high gradient dB/dt exposure. Clinical evaluation of the pacemaker system function occurred immediately before and after MRI, 1 week and 1 month post-MRI, and at corresponding times for the control group. Primary endpoints for safety analyzed the MRI procedure complication-free rate and for effectiveness compared capture and sensing performance between MRI and control groups.
No MRI-related complications occurred during or after MRI, including sustained ventricular arrhythmias, pacemaker inhibition or output failures, electrical resets, or other pacemaker malfunctions. Pacing capture threshold and sensed electrogram amplitude changes were minimal and similar between study groups.
This trial documented the ability of this pacemaker system to be exposed in a controlled fashion to MRI in a 1.5 T scanner without adverse impact on patient outcomes or pacemaker system function.
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.
The effects of dopaminergic therapy for Parkinson's disease (PD) on the brain functional architecture are still unclear. We investigated this topic in 31 PD patients (disease duration: 11.2 ± (SD) ...3.6 years) who underwent clinical and MRI assessments under chronic dopaminergic treatment (duration: 8.3 ± (SD) 4.4 years) and after its withdrawal. Thirty healthy controls were also included. Functional and morphological changes were studied, respectively, with eigenvector centrality mapping and seed-based connectivity, and voxel-based morphometry. Patients off medication, compared to controls, showed increased connectivity in cortical sensorimotor areas extending to the cerebello-thalamo-cortical pathway and parietal and frontal brain structures. Dopaminergic therapy normalized this increased connectivity. Notably, patients showed decreased interconnectedness in the medicated compared to the unmedicated condition, encompassing putamen, precuneus, supplementary motor and sensorimotor areas bilaterally. Similarly, lower connectivity was found comparing medicated patients to controls, overlapping with the within-group comparison in the putamen. Seed-based analyses revealed that dopaminergic therapy reduced connectivity in motor and default mode networks. Lower connectivity in the putamen correlated with longer disease duration, medication dose, and motor symptom improvement. Notably, atrophy and connectivity changes were topographically dissociated. After chronic treatment, dopaminergic therapy decreases connectivity of key motor and default mode network structures that are abnormally elevated in PD off condition.
Background
Neonates and young children require efficacious magnetic resonance imaging (MRI) examinations but are potentially more susceptible to the short- and long-term adverse effects of ...gadolinium-based contrast agents due to the immaturity of their body functions.
Objective
To evaluate the acute safety and diagnostic efficacy of gadoteridol (ProHance) for contrast-enhanced MRI of the central nervous system (CNS) in children ≤2 years of age.
Materials and methods
One hundred twenty-five children ≤2 years old (including 57 children <6 months old) who underwent contrast-enhanced MRI of the CNS with gadoteridol at 0.1 mmol/kg body weight were retrospectively enrolled at five imaging centers. Safety data were assessed for acute/subacute adverse events in the 48 h following gadoteridol administration and, when available, vital signs, electrocardiogram (ECG) and clinical laboratory values obtained from blood samples taken from 48 h before until 48 h following the MRI exam. The efficacy of gadoteridol-enhanced MRI compared to unenhanced MRI for disease diagnosis was evaluated prospectively by three blinded, unaffiliated readers.
Results
Thirteen changes of laboratory values (11 mild, 1 moderate, 1 unspecified) were reported as adverse events in 7 (5.6%) patients. A relationship to gadoteridol was deemed possible though doubtful for two of these adverse events in two patients (1.6%). There were no clinical adverse events, no serious adverse events and no clinically meaningful changes in vital signs or ECG recordings. Accurate differentiation of tumor from non-neoplastic disease, and exact matching of specific MRI-determined diagnoses with on-site final diagnoses, was achieved in significantly more patients by each reader following the evaluation of combined pre- and post-contrast images compared to pre-contrast images alone (84.6–88.0% vs. 70.9–76.9%;
P
≤0.006 and 67.5–79.5% vs. 47.0–66.7%;
P
≤0.011, respectively).
Conclusion
Gadoteridol at 0.1 mmol/kg body weight is safe, well tolerated and effective for contrast-enhanced MRI of the CNS in children ≤2 years of age.
This study was an initial phase II trial in humans of molecular magnetic resonance (MR) imaging for improved visualization of thrombi in vessel territories potentially responsible for stroke using a ...new fibrin-specific contrast agent (EP-2104R). Eleven patients with thrombus in the left ventricle (
n
= 2), left or right atrium (
n
= 4), thoracic aorta (
n
= 4) or carotid artery (
n
= 1) as verified by an index examination (ultrasound, computed tomograpy, or conventional MR) were enrolled. All MR imaging was performed on 1.5 T whole-body MR-system using an inversion-recovery black-blood gradient-echo sequence. The same sequence was performed before and 2–6 h after low-dose intravenous administration of 4 μmol/kg EP-2104R. Two investigators assessed image quality and signal amplification. Furthermore, contrast-to-noise ratios (CNR) between the clot and the blood pool/surrounding soft tissue before and after administration of the contrast agent were compared using Student’s
t
-test. MR imaging and data analysis were successfully completed in 10 patients. No major adverse effects occurred. On enhanced images, thrombi demonstrated high signal amplification, typically at the clot surface, with a significantly increased contrast in comparison to the surrounding blood pool and soft tissue (CNR for clot vs. blood pool, unenhanced and enhanced: 6 ± 8 and 29 ± 14; CNR for clot vs. soft tissue, unenhanced and enhanced: 0 ± 4 and 21 ± 13;
P
< 0.01 for both comparisons). EP-2104R allows for molecular MR imaging of thrombi potentially responsible for stroke. High contrast between thrombus and surrounding blood and soft tissues can be achieved with enhanced imaging.
Summary
Objective The Leksell gamma knife (LGK) is one of the treatment options for pituitary adenomas. We report on our long‐term experience treating acromegaly using LGK.
Design Since 1993 we ...have followed 96 acromegaly patients through periods of from 12 to 120 months. The mean follow‐up period was 53·7 ± 26·8 months. Seventy‐two patients were treated with neurosurgery prior to LGK; for 24 LGK was the primary treatment. Thirteen patients were irradiated twice, due to persistent activity of the adenoma or its residue. Pituitary functions were tested at 6‐month intervals, post‐irradiation. The target tumour volume for radiosurgery was between 93·3 and 12 700 mm3 (median 1350 mm3).
Results Fifty per cent of the patients achieved mean GH < 2·5 µg/l within 42 months, normalized their IGF‐I within 54 months, and achieved GH suppression in the oral glucose tolerance test (oGTT) < 1 µg/l with normal IGF‐I within 66 months. LGK effectiveness was dependent on initial adenoma hormonal activity (GH and IGF‐I serum levels), not on the size of the adenoma. Patients with primary neurosurgery followed by LGK irradiation had better outcomes than those with LGK alone. Irradiation arrested all adenoma growth, causing tumour shrinkage in 62·3% of patients. Twenty‐six developed hypopituitarism when irradiated by 15 Gy (or more) on functional peritumoral pituitary tissue. No hypopituitarism appeared using lower doses.
Conclusions In acromegaly, LGK is a useful adjunct to primary neurosurgery when treating post‐surgical residues because it can limit the duration of medical therapy. It can be used as a primary therapy when neurosurgery is not possible.
Purpose
Stereotactic radiosurgery is one of the treatment options for prolactinomas, the most commonly used being Gamma Knife Radiosurgery (GKRS). GKRS is indicated mainly in the treatment of ...dopamine agonist (DA)-resistant prolactinomas. In our study, we report on our experience in treating prolactinoma patients by GKRS.
Methods
Twenty-eight patients were followed-up after GKRS for 26–195 months (median 140 months). Prior to GKRS, patients were treated with DAs and 9 of them (32.1%) underwent previous neurosurgery. Cavernous sinus invasion was present in 16 (57.1%) patients. Indications for GKRS were (i) resistance to DA treatment (17 patients), (ii) drug intolerance (5 patients), or (iii) attempts to reduce the dosage and/or shorten the length of DA treatment (6 patients).
Results
After GKRS, normoprolactinaemia was achieved in 82.1% of patients, out of which hormonal remission (normoprolactinaemia after discontinuation of DAs) was achieved in 13 (46.4%), and hormonal control (normoprolactinaemia while taking DAs) in 10 (35.7%) patients. GKRS arrested adenoma growth or decreased adenoma size in all cases. Two patients (8.3%) developed hypopituitarism after GKRS. Prolactinoma cystic transformation with expansive behaviour, manifested by bilateral hemianopsia, was observed in one patient.
Conclusions
GKRS represents an effective treatment option, particularly for DA-resistant prolactinomas. Normoprolactinaemia was achieved in the majority of patients, either after discontinuation of, or while continuing to take, DAs. Tumour growth was arrested in all cases. The risk of the development of hypopituitarism can be limited if the safe dose to the pituitary and infundibulum is maintained.
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