Parallel transmit 7T MRI for adult epilepsy pre-surgical evaluation

Publication: Epilepsia

Krzysztof KlodowskiMinghao ZhangJian P. JenDaniel J. ScoffingsRobert MorrisVictoria LupsonFranck MauconduitAurélien MassireVincent GrasNicolas BoulantChristopher T. RodgersThomas E. Cope

20 March 2025

The aim of the study was to implement parallel transmit (pTx) 7T magnetic resonance imaging (MRI) in the pre-surgical evaluation of 3T-negative patients with drug-resistant focal epilepsy, and to compare quality to conventional single transmit (specifically, circularly polarized [CP]) 7T MRI.

We implemented a comparative protocol comprising both pTx and CP 7T MRI in consecutive adult candidates for epilepsy surgery who had negative or equivocal 3T MRI imaging. Here we report the outcomes from the first 31 patients. We acquired pTx and CP T1, T2, fluid-attenuated inversion recovery (FLAIR) and edge-enhancing gradient echo (EDGE) images, all in the same three-dimensional (3D) 0.8 mm isotropic space. Two-dimensional (2D) high-resolution T2 and T2*-weighted sequences were acquired only in CP mode due to current technological limitations. Two neuroradiologists, a neurologist, and a neurosurgeon made independent, blinded quality and preference ratings of pTx vs CP images. Quantitative methods were used to assess signal dropout.

7T revealed previously-unseen structural lesions in nine patients (29%), confirmed 3T-equivocal lesions in four patients (13%), and disproved 3T-equivocal lesions in four patients (13%). Lesions were better visualized on pTx than CP in 57% of cases, and never better visualized on CP. Clinical management was altered by 7T in 18 cases (58%). Nine cases were offered surgical resection and one laser interstitial thermal therapy (LITT). Three cases were removed from the surgical pathway because of bilateral or extensive lesions. Five cases were offered stereo-electroencephalography (sEEG) with better targeting (in three because the 7T lesion was deemed equivocal by the multi-disciplinary team (MDT), and in two because the lesion was extensive). Blinded comparison confirmed significantly better overall quality of pTx FLAIR images (F(2, 184) = 13.7, p = 2.88 × 10−6), whereas pTx MP2RAGE images were subjectively non-inferior and had improved temporal lobe coverage with quantitatively less signal drop-out.

pTx-7T is implementable in a clinical pathway, changed management in 58% of patients where 3T + FDG-PET had not enabled resection, and is superior to single transmit 7T MRI.

Key points

  • We scanned 31 patients with parallel transmit and conventional 7T magnetic resonance imaging (MRI), finding previously-unreported structural lesions in nine patients (29% of cases).
  • In 13% of cases, 7T MRI showed that an equivocal lesion at 3T MRI was likely significant
  • In 13% of cases, 7T MRI showed that an equivocal lesion at 3T MRI could be disregarded.
  • Both qualitative and quantitative quality assessments indicate superiority of pTx images over circularly polarized (CP).
  • Future clinical implementations of 7T MRI for epilepsy should utilize parallel transmit where possible.

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Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities

Publication: Nature

Douglas P. Loesch, Manik Garg, Dorota Matelska, Dimitrios Vitsios, Xiao Jiang, Scott C. Ritchie, Benjamin B Sun, Heiko Runz, Christopher D. Whelan, Ruey R. Holman, Robert J. Mentz, Filipe A. Moura, Stephen D. Wiviott, Marc S Sabatine, Miriam S Udler, Ingrid A. Gause-Nilsson, Slavé Petrovski, Jan Oscarsson, Abhishek Nag, Dirk S. Paul & Michael Inouye.

03 March 2025

Genomics can provide insight into the etiology of type 2 diabetes and its comorbidities, but assigning functionality to non-coding variants remains challenging. Polygenic scores, which aggregate variant effects, can uncover mechanisms when paired with molecular data. Here, we test polygenic scores for type 2 diabetes and cardiometabolic comorbidities for associations with 2,922 circulating proteins in the UK Biobank. The genome-wide type 2 diabetes polygenic score associates with 617 proteins, of which 75% also associate with another cardiometabolic score. Partitioned type 2 diabetes scores, which capture distinct disease biology, associate with 342 proteins (20% unique). In this work, we identify key pathways (e.g., complement cascade), potential therapeutic targets (e.g., FAM3D in type 2 diabetes), and biomarkers of diabetic comorbidities (e.g., EFEMP1 and IGFBP2) through causal inference, pathway enrichment, and Cox regression of clinical trial outcomes. Our results are available via an interactive portal (https://public.cgr.astrazeneca.com/t2d-pgs/v1/).

 

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Endoscopic, ultrasound-guided, radiofrequency ablation of aldosterone-producing adenomas (FABULAS): a UK, multicentre, prospective, proof-of-concept trial

Publication: The Lancet

Giulia Argentesi, Xilin Wu, Alexander Ney, Emily Goodchild, Kate Laycock, Yun-Ni Lee, Russell Senanayake, James MacFarlane, Elizabeth Ng, Jessica Kearney, Sam O’Toole, Jackie Salsbury, Nick Carroll, Daniel Gillett, John A Tadross, Alison Marker, Edmund M Godfrey, George Goodchild, Jonathan P Bestwich, Prof Mark Gurnell, Heok Cheow, Prof Stephen P. Periera, Prof William M Drake, Prof Morris J Brown, FABULAS Study Group

07 February 2025

Five percent of all cases of hypertension are caused by the potentially curable cause – unilateral aldosterone-producing adrenal adenomas (APAs). Very often their localisation (via adrenal vein sampling – AVS) and removal (by laparoscopic adrenalectomy) are not appealing to patients. Another, less invasive,  method of detecting and treating APAs has been discovered by the FABULAS Study Group. Over a five year testing period, 44 patients were screened and 28 recruited. The recruited patients  underwent ablations using the new EUS-RFA technology with positive outcomes; complete or partial biochemical cure in 21 participants and complete or partial cure of hypertension in 12 participants after a 3 month period. These findings appear to offer a safe alternative to total adrenalectomy for the treatment of left sided APAs and could potentially cure primary aldosteronism and hypertension when most of the APA is ablated.

GABAergic modulation of beta power enhances motor adaptation in frontotemporal lobar degeneration

Publication: Alzheimers & Dementia: The Journal of Alzheimer’s Association

Laura Hughes, Natalie E. Adams, Matthew A. Rouse, Michelle Naessens, Alexander Shaw, Alexander G. Murley, Thomas E. Cope, Negin Holland, David Nesbitt, Duncan Street, David J. Whiteside, James B. Rowe. 

19 February 2025

Study examined how abnormal prefrontal neurophysiology and changes in gamma-aminobutyric acid-ergic (GABAergic) neurotransmission contribute to behavioral impairments in disorders associated with frontotemporal lobar degeneration (FTLD).

Magnetoencephalography was recorded during an adaptive visuomotor task from 11 people with behavioral-variant frontotemporal dementia, 11 with progressive supranuclear palsy, and 20 age-matched controls. Tiagabine, a gamma-aminobutyric acid (GABA) re-uptake inhibitor, was used as a pharmacological probe to assess the role of GABA during motor-related beta power changes.

Task impairments were associated with diminished movement-related beta power. Tiagabine facilitated partial recovery of behavioral impairments and neurophysiology, moderated by executive function, such that the greatest improvements were seen in those with higher cognitive scores. The right prefrontal cortex was revealed as a key site of drug interaction.
Behavioral and neurophysiological deficits can be mitigated by enhancement of GABAergic neurotransmission.

Clinical trials are warranted to test for enduring clinical benefits from this restorative-psychopharmacology strategy.


Highlights

  • Event-related beta power changes during movement can be altered by the GABA reuptake inhibitor, tiagabine.
  • In people with behavioral-variant frontotemporal dementia and progressive supranuclear palsy, tiagabine enhanced beta modulation and concurrently improved task performance, dependent on baseline cognition, and diagnosis.
  • The effects of the drug suggest a GABA-dependent beta-related mechanism that underlies adaptive motor control.
  • Restoring selective deficits in neurotransmission is a potential means to improve behavioral symptoms in patients with dementia.

 

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Humoral responses to SARS-CoV-2 vaccine in vasculitis-related immune suppression


Publication
: Science Advances


Kimia Kamelian, Benjamin Sievers, Michael Chen-Xu, Sam Turner, Mark Tsz, Kin Cheng, Mazharul Altaf, Steven A. Kemp, Adam Abdullahi, Kata Csiba, Dami A. Collier, Petra Mlcochova, Bo Meng, Rachel B. Jones, The CITIID-NIHR BioResource COVID-19 Collaboration, Derek Smith, John Bradley, Kenneth G. C. Smith, Rainer Doffinger, Rona M. Smith and Ravindra K. Gupta.

12 February 2025


Immune suppression poses a challenge to vaccine immunogenicity. We show that serum antibody neutralization against SARS-CoV-2 Omicron descendants was largely absent post-doses 1 and 2 in individuals with vasculitis treated with rituximab. Detectable and increasing neutralizing titers were observed post-doses 3 and 4, except for XBB. Rituximab in vasculitis exacerbates neutralization deficits over standard immunosuppressive therapy, although impairment resolves over time since dosing. We observed discordance between detectable IgG binding and neutralizing activity specifically in the context of rituximab use, with high proportions of individuals showing reasonable IgG titer but no neutralization. ADCC response was more frequently detectable compared to neutralization in the context of rituximab, indicating that a notable proportion of binding antibodies are non-neutralizing. Therefore, use of rituximab is associated with severe impairment in neutralization against Omicron descendants despite repeated vaccinations, with better preservation of non-neutralizing antibody activity.

 

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Predisposition Footprints in the Somatic Genome of Wilms tumour

Publication: Cancer Discovery

Approximately 10% of children with cancer harbour a mutation in a predisposition gene. In children with the kidney cancer Wilms tumour, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumorigenesis. This cohort study found that tumour development differed in children harbouring a predisposition, depending on the variant gene and its developmental timing. Treatment may therefore require a variant-specific approach. Overall, findings showed that certain predispositions dictate the genetic development of tumours, with clinical implications for these children.

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Deconstructing delay discounting in human cocaine addiction using computational modelling and neuroimaging

Publication: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

Michal M Graczyk, Rudolf N Cardinal, Tsen Vei Lim, Salvatore Nigro, Elijah Mak, Karen D Ersche

26 December 2024

A preference for sooner-smaller over later-larger rewards, known as delay discounting, is a candidate transdiagnostic marker of waiting impulsivity and a research domain criterion. While abnormal discounting rates have been associated with many psychiatric diagnoses and abnormal brain structure, the underlying neuropsychological processes remain largely unknown. Here, we deconstruct delay discounting into choice and rate processes by testing different computational models and investigate their associations with white matter tracts.

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Peripheral innate immunophenotype in neurodegenerative disease: blood-based profiles and links to survival

Publication: Nature

Alexandra Strauss, Peter Swann, Stacey L. Kigar, Rafailia Christou, Natalia Savinykh Yarkoni, Lorinda Turner, Alexander G. Murley, Leonidas Chouliaras, Noah Shapiro, Nicholas J. Ashton, George Savulich, W. Richard Bevan-Jones, Ajenthan Surendranthan, Kaj Blennow, Henrik Zetterberg, John T. O’Brien, James B. Rowe & Maura Malpetti

29 October 2024

Summary

The innate immune system plays an integral role in the progression of many neurodegenerative diseases. In addition to central innate immune cells (e.g., microglia), peripheral innate immune cells (e.g., blood monocytes, natural killer cells, and dendritic cells) may also differ in these conditions. However, the characterization of peripheral innate immune cell types across different neurodegenerative diseases remains incomplete. This study aimed to characterize peripheral innate immune profiles using flow cytometry for immunophenotyping of peripheral blood mononuclear cells.

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Efficacy of Air Cleaning Units for preventing SARS-CoV-2 and other hospital-acquired infections on medicine for older people wards: A quasi-experimental controlled before-and- after study

Publication: Journal of Hospital Infection

Rebecca C. Brock, Robert J.B. Goudie, Christine Peters, Rachel Thaxter, Theodore Gouliouris, Christopher J.R. Illingworth, Andrew Conway Morris, Clive B. Beggs, Matthew Butler, Victoria L. Keevil

5 October 2024

Summary

Researchers have been leading the Addenbrookes Air Disinfection Study (AAirDS) looking at whether Air Cleaning Units in hospital wards reduce hospital-acquired infections, particularly COVID-19.

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Quantitative susceptibility mapping at 7 T in COVID-19: brainstem effects and outcome associations 

Publication: Brain

Catarina Rua, Betty Raman, Christopher T Rodgers, Virginia F J Newcombe, Anne Manktelow, Doris A Chatfield, Stephen J Sawcer, Joanne G Outtrim, Victoria C Lupson, Emmanuel A Stamatakis, Guy B Williams, William T Clarke, Lin Qiu, Martyn Ezra, Rory McDonald, Stuart Clare, Mark Cassar, Stefan Neubauer, Karen D Ersche, Edward T Bullmore, David K Menon, Kyle Pattinson, James B Rowe 

08 October 2024

Summary

Damage to the brainstem – the brain’s ‘control centre’ – is behind long-lasting physical and psychiatric effects of severe Covid-19 infection, a study suggests.

Using ultra-high-resolution scanners that can see the living brain in fine detail, researchers from the Universities of Cambridge and Oxford and supported by NIHR Cambridge and Oxford BRCs, were able to observe the damaging effects Covid-19 can have on the brain. Read the full news story.

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