Establishment of a calibration sample for the evaluation of MRI perfusion measurement of cerebral blood flow at the individual case level: further development of the imaging-based differential diagnosis of dementia syndromes
Organizational Data
- DRKS-ID:
- DRKS00033740
- Recruitment Status:
- Recruiting ongoing
- Date of registration in DRKS:
- 2024-03-04
- Last update in DRKS:
- 2024-05-02
- Registration type:
- Prospective
Acronym/abbreviation of the study
No Entry
URL of the study
No Entry
Brief summary in lay language
In this study, 180 healthy subjects aged between 50 and 80 years are examined in order to establish a reference for brain perfusion. The subjects are selected according to gender and age groups. For an equivalence test between two imaging methods (MR-based perfusion measurement and FDG-PET), 60 subjects will be randomly selected. Participation in the FDG-PET examinations is voluntary. The MR perfusion measurement is performed with a pCASL sequence and the measurement protocol includes different MR sequences. Study participants must fulfil certain criteria, such as age between 50-80 years, absence of neurological or psychiatric diseases, and others. The sample size was estimated by the TOST procedure for equivalence testing, with an equivalence interval and fixed significance limits. The MRI exclusion criteria include certain medical conditions and implants. MR-based perfusion measurement is performed using continuous arterial spin labelling (CASL) technique, quantifying regional cerebral blood flow. The parameters for perfusion measurement are described in detail. The data is analysed using software packages and the results are compared in the stereotactic standardised room. In addition, 18F-FDG-PET examinations will be performed to analyse similarities or differences with MR-based perfusion measurement. The study aims to perform a comprehensive assessment of brain perfusion and to test the equivalence of MR perfusion and FDG-PET, with the advantage of performing both examinations simultaneously.
Brief summary in scientific language
This study aims to establish a reference for brain perfusion by examining a total of 180 neurologically healthy participants using MR-based perfusion measurement. The sample will be gender-balanced across the three most crucial decades (50–80 years) for Alzheimer's diagnostics. Based on prior clinical experiences, not all 180 participants need to undergo FDG-PET measurements for the intended equivalence study. Calculations suggest a sample size of 60 individuals, randomly selected for representativeness from both gender and age groups. Specifically, 10 participants are allocated for each combination of gender and age, emphasizing the voluntary nature of participation in additional FDG-PET examinations. For each of the three age decades, 30 male and 30 female participants are planned, with the sample size chosen based on the central limit theorem, expecting the distribution of mean rCBF values per decade to follow normal distribution. The study also plans simultaneous 18F-FDG-PET measurements, aiming to evaluate method equivalence. Data analysis involves the use of Statistical Parametric Mapping (SPM12) and MATLAB for preprocessing and statistical evaluation. Individual-level qualitative assessment involves visual comparison of 3D color maps by three independent observers. The study design ensures simultaneous MR-based perfusion and 18F-FDG-PET measurements under identical conditions, allowing for a comprehensive evaluation of similarities and potential differences between the two imaging methods.
Health condition or problem studied
- Free text:
- The scientific question of the described research programme deals with the improvement of the early diagnosis of neurodegenerative diseases, especially dementia, through the further development and use of multimodal PET/MRI imaging techniques. The main aim of the project is to increase diagnostic accuracy and efficiency in order to enable more valid and reliable identification of patients with incipient memory impairment, particularly in relation to Alzheimer's disease.
- Healthy volunteers:
- Yes
Interventions, Observational Groups
- Arm 1:
- Study group: The scientific question of the described research program deals with the improvement of early diagnosis of neurodegenerative diseases, especially dementia, by the further development and use of multimodal PET/MRI imaging techniques. The project's main goal is to increase diagnostic accuracy and efficiency to enable a more valid and reliable identification of patients with incipient memory impairment, especially in relation to Alzheimer's disease. The research is based on the fact that dementias, including Alzheimer's disease, are associated with specific pathophysiological changes in the brain, including the abnormal accumulation of protein fragments (neurofibrillary tangles and plaques). These changes can be visualised on imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI). PET imaging can detect specific biomarkers such as amyloid-β and tau protein deposits, while MRI imaging can measure brain perfusion (blood flow). The research programme aims to optimise the conventional triple diagnostic method (AT(N) biomarker diagnostics), which is based on the detection of amyloid-β, tau protein and neurodegenerative changes. It is being investigated whether MRI-based measurement of brain perfusion (MR-ASL) can be used as a substitute for PET imaging with [18F]-fluorodeoxyglucose (18F-FDG) to achieve similarly accurate diagnostic results. This approach could reduce diagnostic time and increase patient comfort and safety. Specifically, the following objectives are to be achieved: 1. Establish a reference standard for MR-based brain perfusion: The first main objective is to establish a norm distribution for regional brain perfusion using the MR-ASL method in the healthy brain. This norm distribution will serve as a reference to identify deviations in patients with memory impairment. 2. Comparison of diagnostic equivalence: The research program intends to test the diagnostic equivalence between MR-ASL measurement and conventional [18F]-FDG-PET imaging. This will likely require extensive analysis of individual-level data to determine whether the MR-ASL method can provide similarly accurate information on brain activity and perfusion as [18F]-FDG-PET imaging. 3. Expansion of the diagnostic triage: if diagnostic equivalence is successfully confirmed, the MR-ASL method could replace [18F]-FDG-PET imaging in the diagnostic triage, which could reduce examination time and increase patient safety. 4. Significance for research and clinical practice: If the study is successful, it could provide a solid basis for further research projects in the field of neurodegenerative diseases and improve early clinical diagnosis. Overall, the research program aims to use innovative imaging techniques to optimize the diagnosis of dementia while increasing patient comfort and safety. This could represent a significant advance in the early diagnosis and treatment of these widespread and severe neurological diseases.
Endpoints
- Primary outcome:
- Correlation between F-18 FDG-PET activity and ASL perfusion
- Secondary outcome:
- Differences between the sexes and the age decades
Study Design
- Purpose:
- Prevention
- Retrospective/prospective:
- Prospective
- Study type:
- Non-interventional
- Longitudinal/cross-sectional:
- Cross-sectional study
- Study type non-interventional:
- Epidemiological study
Recruitment
- Recruitment Status:
- Recruiting ongoing
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
-
- Medical center Universitätsklinikum Ulm Ulm
Recruitment period and number of participants
- Planned study start date:
- 2024-03-15
- Actual study start date:
- 2024-05-01
- Planned study completion date:
- 2026-10-01
- Actual Study Completion Date:
- No Entry
- Target Sample Size:
- 180
- Final Sample Size:
- No Entry
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- 50 Years
- Maximum Age:
- 80 Years
- Additional Inclusion Criteria:
- Age: between 50-80 years Absence of neurological or psychiatric disorders, especially epilepsy, migraine, chronic tension headaches Absence of severe or chronic physical illness Absence of use of psychotropic substances Absence of pregnancy High-grade stenosis of the neck vessels (>70 %)
Exclusion Criteria
MRI exclusion criteria: - Hydrocephalus shunt - Metal implants in the head and/or body - Condition after severe craniocerebral trauma or after surgery for brain tumours brain tumours - Pacemaker - Absence of a declaration of consent Exclusion criteria for 18(F)-FDG PET examination: - The blood glucose level is determined before the FDG injection. In case of hyperglycaemia, FDG uptake may be reduced. If the glucose level is above 150-200 mg/dl, the examination cannot be performed or or at a later time after the glucose level has been checked again. - Presence of pregnancy - Because the FDG-PET examination is performed in the magnetic field of the PET /MRI device, all MRI-related exclusion criteria also apply (see exclusion criteria also apply (see above).
Addresses
Primary Sponsor
- Address:
- Klinik für Nuklearmedizin, Universitätsklinikum Ulm89081 UlmGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Klinik für Nuklearmedizin, Universitätsklinikum UlmDr. med. Joachim StrobelAlbert-Einstein-Allee 2389081 UlmGermany
- Telephone:
- +49 731 500 61301
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.uniklinik-ulm.de/nuklearmedizin.html
Contact for Public Queries
- Address:
- Klinik für Nuklearmedizin, Universitätsklinikum UlmDr. med. Joachim StrobelAlbert-Einstein-Allee 2389081 UlmGermany
- Telephone:
- +49 731 500 61301
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- https://www.uniklinik-ulm.de/nuklearmedizin.html
Principal Investigator
- Address:
- Klinik für Nuklearmedizin, Universitätsklinikum UlmÄrztlicher Direktor, Prof. Dr. med. Ambros BeerAlber-Einstein-Allee 2389081 UlmGermany
- Telephone:
- 073150061301
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Sources of Monetary or Material Support
Institutional budget, no external funding (budget of sponsor/PI)
- Address:
- Klinik für Nuklearmedizin, Universitätsklinikum Ulm89081 UlmGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission der Universität UlmOberberghof 789081 UlmGermany
- Telephone:
- +49-731-50022050
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- http://www.uni-ulm.de/einrichtungen/ethikkommission-der-universitaet-ulm/
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- 2022-08-03
- Ethics committee number:
- 239/22
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2022-12-19
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry