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Introduction of High Field Optimized Fast 3D MR Spectroscopic Imaging for IDH Typing of Gliomas and Assisted Surgical Neuro Navigation

English title Introduction of High Field Optimized Fast 3D MR Spectroscopic Imaging for IDH Typing of Gliomas and Assisted Surgical Neuro Navigation
Applicant Slotboom Johannes
Number 182569
Funding scheme Project funding
Research institution University Institute for Diagnostic and Interventional Neuroradiology (SCAN) Inselspital
Institution of higher education University of Berne - BE
Main discipline Structural Research
Start/End 01.08.2019 - 31.07.2023
Approved amount 363'894.00
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All Disciplines (3)

Structural Research
Other disciplines of Physics
Neurophysiology and Brain Research

Keywords (11)

MRI & MRS ; (fast) MRSI; spectral editing; RF-pulse shape optimization; pulse sequence development; pulse sequence testing (in vitro/ in vivo); high field MR; k-space sampling strategies; parallelized spectral quantification; brain and brain tumor metabolism

Lay Summary (German)

Diese Studie versucht herauszufinden welche die meist optimale MR-Spektroskopie Pulssequenz gebraucht werden muss um den IDH-status von Gliome (bestimmte Art HIrtumore) zu bestimmen. Wenn im Tumor Spektrum 2-Hydroxy-Glutarat (2HG) nachgewiesen werden kann, handelt es sich um niedrig gradigen Hirntumor mit lange Überlebenszeit (etwa 7 Jahre)oder einen Hochgradigen Tumor, mit einem Überlebenszeit von nur 15-16 Monaten. Optimale Therapie dieser Tumoren kann mit diese nicht-invasiv erworbene Informationen
Lay summary
Gliome sind die beim Menschen am häufigsten vorkommenden Hirntumore. Es gibt Gliome, die sehr aggressiv sind, und diese Patienten haben eine mittlere Überlebenszeit von etwa 15-16 Monate. Es gibt auch Patienten, die an weniger aggressiven Gliome erkranken, die dann eine mittlere Überlebenszeit von etwa 7 Jahren haben.

Man hat vor nicht allzu langer Zeit festgestellt, dass es genetische Faktoren sind, die bestimmen ob ein Gliom aggressives Wachstum aufweist oder nicht. Zwei der wichtigsten genetischen Faktoren sind die sogenannte „IDH1“ und „IDH2“ Gene. Gliome, die Mutationen (genetische Änderungen) dieser Gene aufweisen, sind weniger aggressiv wachsend; folglich haben diese Patienten eine viel längere mittlere Überlebenszeit.

Bei Patienten mit Verdacht auf ein Gliom ist die Entnahme einer kleinen Gewebeprobe des Tumors die übliche Vorgehensweise. Bei diesem Eingriff allerdings besteht die Gefahr von bakteriellen Infektionen des Gehirns, oder es kann zu Blutungen im Hirn kommen, die schnell zu einer lebensbedrohlichen Situation führen können.

Eine erst kürzlich veröffentlichte Entdeckung zeigt, dass in IDH1 und/oder IDH2 mutierten Gliome eine bestimmte chemische Substanz in viel höhere Konzentration vorkommt als in nicht mutierten Gliome. Diese chemische Substanz ist das sogenannte 2-Hydroxy-Glutarat (2HG). Diese Substanz kann in einem Magnet Resonanz Tomographen (MRT oder „die Röhre“) mit einer Technik, die „Magnet Resonanz Spektroskopie“ (MRS) heisst, direkt gemessen werden, ohne dass man den Patienten operieren muss. Neben dieser Substanz kann man gleichzeitig auch noch verschiedene andere Substanzen messen, die in Gliome und im normalen Hirngewebe vorkommen. Man kann sogar Bilder machen, wo diese Substanzen genau im Hirn und im Hirntumor vorkommen.

Es gibt verschiedene Arten, wie man diese MRS Messungen in einem MR-Tomographen durchführen kann. Das Hauptziel dieser Studie ist herauszufinden, welche Art von MRS-Untersuchung die genaueste Information gibt, um die Aggressivität des Glioms so gut wie möglich zu bestimmen. Diese Information kann dazu verwendet werden, dem Patienten eine optimale Therapie anbieten zu können.
Direct link to Lay Summary Last update: 04.07.2019

Responsible applicant and co-applicants


Name Institute

Project partner

Associated projects

Number Title Start Funding scheme
140958 Establishing Novel MR Criteria for the Assessment of Malignant Glioma Progression 01.10.2012 Project funding


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 80tees, 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 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 our 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 recoded twice at 3T); (viii.) pre-operative application of the best suited EPSI-pulse sequence in a total of 40 patients: 20 patients will be recorded at 3T and 20 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.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 (Sabati et al., 2015), available via Siemens, as well as the CMRR-implementation of the mega-semi-LASER for 2HG-editing (CMRR Spectroscopy Package, (Marjanska et al., 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 (J Slotboom et al., 1998) made available as separate plugin within jMRUI-spectroscopy package. Co-registration of pre-surgery EPSI-data with post-operative structural MRI-data will be performed with SPM. Statistical analysis and machine learning algorithms will be based on statistical programming language “R”.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.