Deriving Cardiac Reference Ranges at 3.0Tesla in Healthy Volunteers (DECADENT-HV)

Current MRI society guidelines recommend that reference ranges for specific imaging techniques (T1, T2 mapping, perfusion) are acquired on the MRI scanner that clinical work and research studies are being carried out on. We propose to undertake 32 multi parametric stress cardiac MRI scans on healthy volunteers (50% female, 50% male) over the age of 18 years. These measurements are not yet available for the 3.0T Prisma scanner at the Institute of Clinical Excellence (ICE), Queen Elizabeth University Hospital (QEUH). These values are essential to identify what is abnormal for people living in the west of Scotland.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Diagnostic test: Multiparametric stress CMR protocol

Detailed Description

Imaging societies recommend that each MRI scanner has a locally-derived reference range for tissue characteristics, notably the longitudinal (T1) and transverse (T2) myocardial relaxation times, measured in milliseconds [16].

T1 reference values vary according to the magnetic field strength of the MRI scanner. T1 and T2 times (ms) are expectedly higher at 3.0T compared to 1.5T, in line with results obtained when working with the Siemens VERIO scanner based at the BHF Glasgow Cardiovascular Research Centre [17]. T2 values for 3.0T are, generally, not so well described and are known to vary between different manufacturers and systems.

A consensus statement by Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI) states that "Reference ranges should be generated from data sets that were acquired, processed, and analyzed in the same way as the intended application, with the upper and lower range of normal defined by the mean plus and minus 2 standard deviations of the normal data, respectively."[16] Myocardial blood flow measurements for both stress and rest are also distinct for individual scanners, especially at 3.0T. In fact, a number of centres have derived site specific and magnet specific reference ranges from healthy volunteers including 1)Stockholm, Sweden, 1.5T Siemens Avanto, 3.4 ± 0.7 ml/min/g [18] 2) Barts (London, UK) 3.0T Siemens Prisma, 3.00 +/-0.76 ml/g/min (unpublished data) and 3) Leeds, UK: 3.0T Siemens Prisma 2.89 ± 0.56 ml/g/min [19], 1.5T Philips Intera, 4.50 ± 0.91 ml/min/g[20] and studies are ongoing in sites such as Oxford (https://www.ouh.nhs.uk/research/patients/trials/stress-mri.aspx) . As can be seen, there is a wide spread of values and local reference ranges are urgently required (defined as stress MBF <2 standard deviations from the mean in healthy volunteers). These measurements are not yet available for the 3.0T Prisma scanner at the Institute of Clinical Excellence (ICE), Queen Elizabeth University Hospital (QEUH). These values are essential to identify what is abnormal for people living in the west of Scotland.

• Study Type: Observational
• Enrollment (Anticipated): 32

Contacts and Locations

• Study Contact: Name: Kenneth Mangion, MD PhD; Phone Number: 0141 232 7600; Email: kenneth.mangion@ggc.scot.nhs.uk

Study Locations

• United Kingdom
  • Lanarkshire
    • Glasgow, Lanarkshire, United Kingdom, G51 4TF
      • Recruiting
      • Queen Elizabeth University Hospital
      • Contact: Kenneth Mangion, MD PhD; Phone Number: 01412327600; Email: kenneth.mangion@ggc.scot.nhs.uk
      • Contact: Robert Sykes, MBChB; Phone Number: 01412327600; Email: robert.sykes@ggc.scot.nhs.uk
      • Principal Investigator: Kenneth Mangion, MD PhD
      • Sub-Investigator: Robert Sykes, MBChB
      • Sub-Investigator: Andrew Morrow, MBChB
      • Sub-Investigator: Colin Berry, MBChB PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers aged at least 18 years with no prior medical history (including cardiovascular health problems, medication or systemic illness including COVID-19) will be invited to participate by i) contacting eligible participants from the Clinical research imaging volunteer bank ii) placing advertisements in public buildings (e.g. hospital, university). Vaccination status for SARS Coronavirus-19 is not an exclusion criterion.

The other exclusion criteria include standard contraindications to MRI (e.g. metallic implants and metallic foreign body) and known or suspected pregnancy.

Description

Inclusion Criteria:

• Age 18≥years
• Capacity to provide written informed consent
• Able to comply with study procedures
• eGFR >45ml/min
• Vaccination status against SARS CoV-19 is not an exclusion criterion.

Exclusion Criteria:

• Contra-indication to CMR e.g. severe claustrophobia, metallic foreign body.
• Contra-indication to intravenous adenosine, i.e. severe asthma; long QT syndrome; second- or third-degree AV block and sick sinus syndrome.
• Lack of informed consent.
• Women who are pregnant, breast-feeding or of child-bearing potential (WoCBP) without a negative pregnancy test
• History of cardiovascular illness.
• Previous COVID-19 illness

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak stress myocardial blood (mg/ml/min)	Peak stress myocardial blood with adenosine vasodilator stress	Through study completion, on average <2years.
Myocardial perfusion reserve	Myocardial perfusion reserve with adenosine vasodilator stress	Through study completion, on average <2years.
Global and septal T1 (MOLLI, shMOLLI) T2	reference ranges	Through study completion, on average <2years.
Global and regional Circumferential strain (GCS)	using Displacement Encoding with Stimulated Echoes (DENSE) MRI.	Through study completion, on average <2years.
Global and regional Longitudinal strain (GLS)	using Displacement Encoding with Stimulated Echoes (DENSE) MRI.	Through study completion, on average <2years.

Collaborators and Investigators

• Sponsor: University of Glasgow
• Collaborators: NHS Greater Glasgow and Clyde

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2021
• Primary Completion (Anticipated): October 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: February 4, 2022
• First Submitted That Met QC Criteria: February 4, 2022
• First Posted (Actual): February 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 4, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: healthy volunteers; strain; cardiovascular magnetic resonance imaging; reference ranges; parametric mapping; adenosine stress
• Other Study ID Numbers: GN20CA408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data sharing will be on reasonable request to the CI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No