Connectivity-guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistent moderate to severe depression: Magnetic resonance imaging protocol and SARS-CoV-2-induced changes for a randomized double-blind controlled trial
AuthorBriley, Paul M.
Liddle, Peter F.
Morriss, Richard K.
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AbstractBackground: Depression is a substantial health and economic burden. In approximately one-third of patients, depression is resistant to first-line treatment; therefore, it is essential to find alternative treatments. Transcranial magnetic stimulation (TMS) is a neuromodulatory treatment involving the application of magnetic pulses to the brain that is approved in the United Kingdom and the United States in treatment-resistant depression. This trial aims to compare the clinical effectiveness, cost-effectiveness, and mechanism of action of standard treatment repetitive TMS (rTMS) targeted at the F3 electroencephalogram site with a newer treatment—a type of TMS called theta burst stimulation (TBS) targeted based on measures of functional brain connectivity. This protocol outlines brain imaging acquisition and analysis for the Brain Imaging Guided Transcranial Magnetic Stimulation in Depression (BRIGhTMIND) study trial that is used to create personalized TMS targets and answer the proposed mechanistic hypotheses. Objective: The aims of the imaging arm of the BRIGhTMIND study are to identify functional and neurochemical brain signatures indexing the treatment mechanisms of rTMS and connectivity-guided intermittent theta burst TMS and to identify imaging-based markers predicting response to treatment. Methods: The study is a randomized double-blind controlled trial with 1:1 allocation to either 20 sessions of TBS or standard rTMS. Multimodal magnetic resonance imaging (MRI) is acquired for each participant at baseline (before TMS treatment) with T1-weighted and task-free functional MRI during rest used to estimate TMS targets. For participants enrolled in the mechanistic substudy, additional diffusion-weighted sequences are acquired at baseline and at posttreatment follow-up 16 weeks after treatment randomization. Core data sets of T1-weighted and task-free functional MRI during rest are acquired for all participants and are used to estimate TMS targets. Additional sequences of arterial spin labeling, magnetic resonance spectroscopy, and diffusion-weighted images are acquired depending on the recruitment site for mechanistic evaluation. Standard rTMS treatment is targeted at the F3 electrode site over the left dorsolateral prefrontal cortex, whereas TBS treatment is guided using the coordinate of peak effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. Both treatment targets benefit from the level of MRI guidance, but only TBS is provided with precision targeting based on functional brain connectivity. Results: Recruitment began in January 2019 and is ongoing. Data collection is expected to continue until January 2023. Conclusions: This trial will determine the impact of precision MRI guidance on rTMS treatment and assess the neural mechanisms underlying this treatment in treatment-resistant depressed patients.
CitationPszczolkowski, S., Cottam, W. J., Briley, P. M., Iwabuchi, S. J., Kaylor-Hughes, C., Shalabi, A., Babourina-Brooks, B., Berrington, A., Barber, S., Di Paolo, A. S., et al. (2022). Connectivity-guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistent moderate to severe depression: Magnetic resonance imaging protocol and SARS-CoV-2-induced changes for a randomized double-blind controlled trial. JMIR Research Protocols, 11(1), pp.e31925.
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To have and to hold: An exploratory qualitative study exploring why research participants with treatment-resistant depression undergoing transcranial magnetic stimulation treatment requested copies of their research brain MRI scansWebster, Lucy; Boutry, Clement; Morriss, Richard K. (2023)PURPOSE: There has been little research providing an in-depth exploration of the reasons behind research participants, particularly in mental health settings, requesting copies of their research data, such as magnetic resonance imaging (MRI) scans. BRIGhTMIND is a large double blind randomised controlled trial using functional and structural magnetic resonance imaging to create personalised targets for transcranial magnetic stimulation delivery, and a number of trial participants requested copies of these scans. METHODS: Seven participants involved in the BRIGhTMIND trial completed semi-structured interviews exploring their reasons behind their request for copies of their MRI scans. The qualitative data was co-analysed between researchers and patient and public involvement and engagement representatives using inductive thematic analysis. RESULTS: The interviews produced consistent themes concerning curiosity to visualise their MRI scans, and the hope that their participation would result in a better understanding of the nature and future treatment of depression. Concerns around the rights to access their own personal health data emerged as a clear theme as did their own ability to interpret any radiological information. DISCUSSION: This study provides insight into the reasons why research participants with depression would like to retain copies of their MRI scans and the perceived role that such techniques may have for improving research and neuromodulation treatments in depression. Such first-hand experiential accounts emphasises the importance of listening to participants perspectives and lived experience, in order to improve research and health outcomes. Future research could aim to provide greater verbal and written information for participants, including details about the accessibility to their MRI scans, the difference between research and clinical MRI scans, and educational materials to help with the interpretation of MRI images.
Impact of MRI on high grade Ductal Carcinoma Insitu (HG DCIS) management, are we using the full scope of MRI?Dakka, Mahmoud (2017-10)Introduction: Preoperative assessment of pure Ductal Carcinoma Insitu (DCIS) is essential in the surgical planning. The role of Magnetic resonance imaging (MRI) has long been debated. The impact of MRI on the management of High Grade (HG) DCIS was assessed, whether it accurately captures the true size of this entity in comparison to conventional imaging, and, if MRI use would reduce the number of re-excision surgery.Method: Ninety-one consecutive patients with HG DCIS, who were identified from a prospectively collected data at Kettering General Hospital between April 2011 and December 2015. All patients had preoperative MRI scan in addition to the standard breast imaging. This was compared to a control group of consecutive patients (n=52) which was obtained from a period just before 2011. Impact on surgical planning and number of surgeries for each patient was compared. The size of HG DCIS estimated by MRI was compared to the final histological size. Secondary outcomes included change of initial surgical plan and detection of occult contralateral breast cancer.Results: MRI group had 91 patients with median age of 63. Seventy percent of which presented through the screening program. The overall sensitivity of MRI to detect HG DCIS was 77% (70/91) with a false negative rate FNR of 23% (21/91). Therefore, 70 patients only were included in the data analysis. The control group included 52 screening patients with comparable baseline characteristics. Re-excision (or completion mastectomy) rates were higher in the control group 26% compared to 8% in the MRI group (P-value 0.012). MRI use correctly converted the initial plan of breast conservation to mastectomy in 9 patients (13%). Five patients had additional ipsilateral malignant features (7%).Occult contra lateral disease, was diagnosed in 2 patients (3%).Conclusion: This study suggests that MRI could be an important tool in reducing the re-excision rates in the surgical management of HG DCIS. Although still controversial, selective MRI imaging can be useful in the preoperative diagnosis and evaluation of HG DCIS. Case by case discussion at MDT is crucial. Wider adaptation of MRI when indicated in the assessment of breast lesions with proper correlation to histology postoperatively is a key in improving our MRI interpretation skills, helping us to exploit the full scope of this useful tool.
Multiparametric Renal Magnetic Resonance Imaging: Validation, Interventions, and Alterations in Chronic Kidney Disease.Mahmoud, Hudu; Taal, Maarten; Selby, Nicholas (2017-09)Background: This paper outlines a multiparametric renal MRI acquisition and analysis protocol to allow non-invasive assessment of hemodynamics (renal artery blood flow and perfusion), oxygenation (BOLD T2(*)), and microstructure (diffusion, T1 mapping). Methods: We use our multiparametric renal MRI protocol to provide (1) a comprehensive set of MRI parameters [renal artery and vein blood flow, perfusion, T1, T2(*), diffusion (ADC, D, D(*), fp), and total kidney volume] in a large cohort of healthy participants (127 participants with mean age of 41 ± 19 years) and show the MR field strength (1.5 T vs. 3 T) dependence of T1 and T2(*) relaxation times; (2) the repeatability of multiparametric MRI measures in 11 healthy participants; (3) changes in MRI measures in response to hypercapnic and hyperoxic modulations in six healthy participants; and (4) pilot data showing the application of the multiparametric protocol in 11 patients with Chronic Kidney Disease (CKD). Results: Baseline measures were in-line with literature values, and as expected, T1-values were longer at 3 T compared with 1.5 T, with increased T1 corticomedullary differentiation at 3 T. Conversely, T2(*) was longer at 1.5 T. Inter-scan coefficients of variation (CoVs) of T1 mapping and ADC were very good at <2.9%. Intra class correlations (ICCs) were high for cortex perfusion (0.801), cortex and medulla T1 (0.848 and 0.997 using SE-EPI), and renal artery flow (0.844). In response to hypercapnia, a decrease in cortex T2(*) was observed, whilst no significant effect of hyperoxia on T2(*) was found. In CKD patients, renal artery and vein blood flow, and renal perfusion was lower than for healthy participants. Renal cortex and medulla T1 was significantly higher in CKD patients compared to healthy participants, with corticomedullary T1 differentiation reduced in CKD patients compared to healthy participants. No significant difference was found in renal T2(*). Conclusions: Multiparametric MRI is a powerful technique for the assessment of changes in structure, hemodynamics, and oxygenation in a single scan session. This protocol provides the potential to assess the pathophysiological mechanisms in various etiologies of renal disease, and to assess the efficacy of drug treatments.