Metabolic Characterization of Space Occupying Lesions of the Brain

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT04233788

Studienbeginn:
September 2021

Letztes Update:
30.01.2023

Wirkstoff:
-

Indikation (Clinical Trials):
Brain Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Insel Gruppe AG, University Hospital Bern

Collaborator:
Swiss National Science Foundation

Studienleiter

Johannes Slotboom, PhD
Study Chair
University of Bern

Kontakt

Johannes Slotboom, PhD
Kontakt:
Phone: +41316327469
E-Mail: johannes.slotboom@gmail.com» Kontaktdaten anzeigen

Marwan El-Koussy, MD
Kontakt:
Phone: +41316320008
E-Mail: marwan.el-koussy@insel.ch» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

Institute for Diagnostic and Interventional Neuroradiology, University Hospital Bern
3010 Bern
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Johannes Slotboom, PhD
Phone: +41316327469
E-Mail: johannes.slotboom@insel.ch» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

Introduction - Recently the first commercially available 7T MR-scanner which is approved for

clinical use came on to the market. The main motivation to go to higher field strengths is

the fact that better SNR can be achieved in shorter acquisition time, or higher spatial

resolution can be obtained in the same measurement time. High field MRI also has drawbacks,

e.g. substantially higher specific absorption rate (SAR), higher susceptibility related image

distortion problems, and longer longitudinal relaxation times. Nevertheless, moving to higher

fields is especially beneficial for MR-spectroscopy. This is due to the fact that better

signal to noise ration (SNR) is combined with higher spectral resolution. The two most

commonly used techniques for spectroscopic imaging (MRSI) are: (i.) relative slow 2D/3D

techniques like PRESS and semiLASER based techniques, and (ii.) fast 3D echo planar based

(EPI) techniques. Although echo planar spectroscopic imaging (EPSI) is a technique that has

been introduced by Sir Peter Mansfield in the first half of 80es, the method is still

continuously being improved, and recently very promising applications related to brain tumor

diagnostics were published. To be mentioned in this context is the fact that the method can

be combined with spectral editing for the detection of 2-hydroxy-glutarate (2HG) in glioma

patients. 2HG is only present if the glioma that has mutations in the IDH-gene. It is shown

that gliomas having the IDH-mutation have a much better overall survival prognosis. Apart

from brain tumor typing, high resolution EPSI imaging also enables investigation the

investigation of tumor infiltration using metabolic criteria. In surgery the patients'

preoperative intake of the 5-aminolevulinic acid (5-ALA) before surgery selectively makes

malignant glioma tissues fluorescent under blue light irradiation and tumor itself becomes

clearly visible during the neurosurgical intervention. The fact that 5-ALA-guided

completely-resected glioma patients have a significant longer survival time, underlines the

necessity to know the exact tumor boundaries.

Aims - The major aims of the study proposed are manifold:

(i.) The development of a novel EPSI-pulse sequence utilizing 3D-radial k-space sampling

schemes, that focuses on robustness w.r.t. patient motion, is robust with respect to chemical

shift displacement artifacts, includes the possibility of 2HG-spectral editing, uses

SAR-reduced radiofrequency (RF) pulses, and operate with total acquisition times that are

acceptable for clinical routine use; (ii.) Comparison of the novel sequence with available

conventional EPSI-techniques and semiLASER-based techniques for clinical routine use

comparing its performance at 3T and 7T; (iii.) The development of a graphic processor unit

(GPU) based fitting algorithm for quantification of 3D-radial EPSI-data based on the existing

tdfdfit-algorithm; (iv.) Extension of a locally developed machine learning based automatic

quality-filtering algorithm to be applied on the researchers' novel EPSI-data; (v.)

Quantitative investigation on the effect spatial non-uniform transmit and receive properties

for all relevant metabolites and spatial dependent signal amplitude correction schemes

(extension of a locally developed method); (vi.) Investigation of the exact effects of

selective excitation on J-coupled spin systems, and comparison of these effects between 3T

and 7T; (vii.) Reproducibility study on 20 healthy volunteers measured twice with the same

protocol (10 recorded twice at 7T and 10 recorded twice at 3T); (viii.) Pre-operative

application of the best suited EPSI-pulse sequence in a total of 75 patients. All patients

will be recorded at 3T as well as at 7T using the equivalent protocols; (ix.) Co-registration

of pre-operative, spatially resolved 3D-EPSI-MRSI data with post-operative 3D-FLAIR and

T1c-imaging in IDH-wildtype patients with had complete resection during 5-ALA guided

neurosurgical interventions will provide information on whether MRSI-techniques are helpful

to predict the tumor affected volume; (x.) Documentation of the location of a biopsy,

histology to enable a better correlation between MR-spectroscopic patterns and histology.

(xi) Comparison of the performance of CEST versus the CMRR-semiLASER MRSI sequence w.r.t. to

the prediction accuracy of the IDH-type of the glioma by the two technologies.

Methodology - The implementation of a robust EPSI sequence that uses 3D-radial k-space

sampling schemes and reconstruction will be performed on Siemens IDEA developer platforms for

VE- and XA-software versions. The sequence will be compared to the performance obtained with

another EPSI implementation, available via Siemens, as well as the CMRR-implementation of the

MEGA (MEscher-GArwood) semi-LASER (Localization by Adiabatic SElective Refocusing) for

2HG-editing (CMRR Spectroscopy Package, 2012). The quantification of the EPSI-data of the

reference sequence will be performed with the MIDAS package. The EPSI-data of the novel

sequence as well as MEGA-semi-LASER sequence will be quantified using a parallelized

GPU-re-implementation of the tdfdfit-algorithm made available as separate plugin within

jMRUI-spectroscopy package (jMRUI: java magnetic resonance user interface). Co-registration

of pre-surgery EPSI-data with post-operative structural MRI-data will be performed with the

SPM (Statistical Parameter Mapping) program. Further statistical analysis and machine

learning algorithms will be based on statistical programming language "R". The CEST pulse

sequences will be obtained via Siemens-Healthineers.

Potential significance - (a.) Pre-surgical knowledge of the IDH-status will enable better

individual neurosurgical treatment of the patient; (b.) Coregistration of metabolic

EPSI-data, with post-operative structural MR-data will give information on the fundamental

usefulness of MRSI-techniques to detect glioma infiltration zones; (c.) Improved follow-up of

IDH-mutated glioma patients, who typically have a long period of minimal progression,

followed rapidly by aggressive growth and transformation to higher grade; (d.) The

availability of an imaging biomarker to monitor tumor recurrence would be a major advance for

all glioma patients.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Healthy people who are able to lie in the MR scanner for one hour;

- Patients with suspected mass in the brain

- Written informed consent

Exclusion Criteria:

- Persons under the age of 18

- Persons who are mentally unable to choose to participate

- Pregnant women

- Patients with oncological findings or neurodegenerative findings in the past

- Wearing active implants (e.g. pacemakers and neurostimulators)

- Emergency patients

- Persons with tattoos on the head or neck area

Studien-Rationale

Primary outcome:

1. Optimal MR-sequence for IDH-typing (Time Frame - 48 months):
Finding the most optimal (2HG-edited, radial kspace-sampled) EPSI MRSI/CEST technique for the initial diagnosis of gliomas with respect to IDH-typing. Pre-operative knowledge of the IDH-type is important information for further neurosurgical treatment.

Secondary outcome:

1. Spectral/CEST pattern (Time Frame - 48 months):
The retrospective analysis of tumor affected tissue volumes identified by 3D-MRSI/CEST image data with the factual resected volumes during 5-ALA guided complete tumor resection interventions enable to find the relationship between the spectral or CEST pattern and the location of the glioma.

Studien-Arme

Sequence optimization (Healthy Control Group 1 (10 Persons))
The MEGA-based editing sequences as well as the SLOW-EPSI sequence will be applied to this group using a 3T Prisma and a 7T Terra scanner. Data will be used for optimization of the pulse sequences. Aim: find those sequence parameters to obtain best spectral quality data (SNR, spatial resolution versus measurement time).
Healthy Control Group 2 (15 Persons)
The best performing sequence which will be applied to this group using a 7T Terra scanner. Data will be used normative data for glutamate/glutamine and GABA levels in healthy controls. Aim: normal reference data for future studies.
Patient Group 1: Comparison of 5 different spectral editing sequences (30 Patients)
Two editing pulse sequence types will be applied to this group at a 3T Prisma and a 7T Terra scanner. The sequences being compared are MEGA-semiLASER-SVS, MEGA-semiLASER based MRSI (on both 3T and 7T) and SLOW-EPSI (on 7T only).
Patient Group 1: Comparison of 4 different CEST sequences (30 Patients)
Two different CEST sequence types will be applied to this group at a 3T Prisma and a 7T Terra scanner. The CEST performance will be compared between 3T and 7T, as well which of the two types in the best on each scanner. Aim: which of the four sequence predicts the IDH-mutation status best.

Geprüfte Regime

MR-scans using a 3T Prisma and a 7T Terra scanner (Siemens, Erlangen Germany) (Examined are fast MRSI sequences and CEST sequences.):
The MR-scans performed at 3T and 7T are performed to evaluate whether high field MR-examinations bring an advantage to the patient in determining the IDH-status of the glioma. Two MRSI/CEST sequences will be tested against each other.

Quelle: ClinicalTrials.gov

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