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Phosphorus MR Spectroscopic Imaging of Brain Tumors at 3T (31P_SPECTRA_3T)

Project Title: Phosphorus MR Spectroscopic Imaging of Brain Tumors at 3T (31P_SPECTRA_3T)

Funded by FP7 Marie Curie International Reintegration Grants (IRG) (2010-2014)

Principal Investigator: Esin Öztürk Işık

Project Summary: Previous studies have shown phosphorus metabolite level differences between brain tumors and healthy brain tissue. When the brain tissue gets ischemic, ATP production comes from hydrolysis of PCr catalyzed by creatine kinase leading to a reduction of PCr:-ATP ratio in 31P MRSI and the breakdown of glycogen to lactic acid which can be observed as the lactate peak in 1H spectra. Pi also increases at ischemia due to increased ATP hydrolysis that is not matched by ATP synthesis leading to a Pi/PCr increase.

Phosphorus MRSI has some major advantages over proton spectroscopic imaging. First, phosphorus spectroscopy does not require any water suppression and it does not have any lipid contamination problems. Second, although the detection of the lactate peak with 1H spectroscopy requires special spectral editing schemes due to the overlapping lipid resonances, 31P spectra can readily display the PCr, Pi, and ATP peaks that can give an assessment of the ischemic state. Tumor growth is associated with both an increased cell membrane synthesis and a higher degradation of cell membranes. Although both membrane synthesis and degradation are evaluated by observing the changes in a single Cho peak in 1H MR spectroscopy, these pathways can be differentiated using 31P MR spectroscopy.

Despite the advantages of 31P-MRSI, it has not been widely used for clinical applications at lower field strengths. The wider availability of high field scanners and multi-channel radiofrequency (RF) surface coils have increased the sensitivity and accuracy of MR imaging and spectroscopy of brain tumors through higher signal-to-noise ratio (SNR) and improved spectral resolution. Increased spectral dispersion at high field results in less overlap between different peaks and simplifies the appearance of the spectrum. Phosphorus MR spectroscopic imaging highly benefits from high field strength with a resulting increase in SNR, better definition of Pi peak, better separation of PC, PE, GPC and GPE peaks, and better estimation of pH values.

The goal of this project is to apply phosphorus magnetic resonance spectroscopic imaging accurately at high-field 3T scanners to add new information regarding the characteristics of brain tumors and produce a new metric that estimates the aggressiveness of a brain tumor using 31P MRSI peak intensities.

Objectives:

  • To estimate the T1 relaxation parameter of phosphorus-containing metabolites within the brain tumor and healthy brain areas at 3T

  • To compare different spectral data analysis strategies to define the most accurate way of quantifying phosphorus spectral data acquired from the human brain at 3T

  • To analyze the spatial heterogeneity and characteristics of brain tumors using 31P MRSI at 3T.

  • To define a metric that can characterize how aggressive a brain tumor is based on the intensities of phosphorus-containing metabolites.

Publications

Phosphorus MR Spectroscopic Imaging

  1. Muhammed Yildirim, Gokce Hale Hatay, Emre Okeer, Klass Nicolay, Bahattin Hakyemez, Esin Ozturk-Isik. Fast Phosphorus MR Spectroscopic Imaging of Human Brain in vivo Using Compressed Sensing at 3T. IEEE EMBS Annual International Conference. Chicago, Illinois, USA, 26-30 August 2014. (poster)

  2. Esin Ozturk-Isik, Gokce Hale Hatay, Emre Okeer, Muhammed Yildirim, Halis Sak, Bahattin Hakyemez. Quantitative Assessment of Phosphorus MR Spectroscopic Imaging Metrics of Brain Tumors in vivo at 3T. IEEE EMBS Annual International Conference. Chicago, Illinois, USA, 26-30 August 2014. (poster)

  3. Citak Er F, Hatay GH, Okeer E, Yildirim, M, Hakyemez B, Ozturk-Isik E. Classification of Phosphorus Magnetic Resonance Spectroscopic Imaging of Brain Tumors Using Support Vector Machine and Logistic Regression at 3T. IEEE EMBS Annual International Conference. Chicago, Illinois, USA, 26-30 August 2014. (oral presentation)

  4. Hatay GH, Okeer E, Hakyemez B, Ozturk-Isik E. Comparison of 2D Iterative Frame Based and 3D Direct Compressed Sensing Reconstruction for Accelerated Phosphorus MR Spectroscopic Imaging of Human Brain. International Society of Magnetic Resonance in Medicine Annual Conference, Milan, Italy, 10-16 May 2014. (traditional poster)

  5. Ökeer E, Hatay GH, Yıldırım M, Çıtak Er F, Öztürk Işık E, Hakyemez B. Two-Dimensional Phosphorus MR Spectroscopic Imaging of Brain Tumors at 3T (Beyin Tümörlerinin 3T Manyetik Alanda İki Boyutlu Fosfor MR Spektroskopik Görüntülenmesi). TMRD 2014. Ankara, Turkey, 22-24 May 2014. (oral presentation)

  6. Hatay GH, Ökeer E, Hakyemez B, Öztürk Işık E. Comparison of 2D iterative frame-based and 3D direct Compressed Sensing Reconstruction for Accelerated Phosphorus MR Spectroscopic Imaging of Human Brain (Hızlandırılmış Fosfor Manyetik Rezonans Spektroskopi ile İnsan Beyninin Görüntülenmesi için İki Boyutlu İteratif ve Üç Boyutlu Direkt Sıkıştırılmış Algılama Yöntemlerinin Karşılaştırılması) TMRD 2014. Ankara, Turkey. 22-24 May 2014. (oral presentation)

  7. Gumus C, Hatay GH, Askin NC, Hakyemez B, Ozturk-Isik E. A Simulation Study for Accelerated Data Acquisition of Phosphorus MR Spectroscopic Imaging of Brain Tumors Using Compressed Sensing. TMRD 2013. Ankara, Turkey. 23-25 May 2013. (oral presentation)

  8. Hatay GH, Gumus C, Hakyemez B, Ozturk-Isik E. Accelerated Phosphorus MR Spectroscopic Imaging of Human Brain Using Compressed Sensing. International Society of Magnetic Resonance in Medicine Annual Conference, Salt Lake City, UT, 19-26 April 2013. Poster number:3810. (traditional poster)

  9. Askin NC, Hakyemez B, Ozturk-Isik E. A Preliminary Simulation Study for Fast Phosphorus MR Spectroscopic Imaging Using Compressed Sensing. Biyomut 2012, Istanbul, Turkey. 3-5 October 2012. Paper number:36. (oral presentation)

  10. Bulut B, Askin NC, Crane JC, Ozturk-Isik E. Quantification of Phosphorus MR Spectroscopic Imaging of Human Brain Using Time Domain Fitting versus Frequency Domain Analysis at 3T. European Society of Magnetic Resonance in Medicine and Biology Annual Conference. Lisbon, Portugal, 4-6 October 2012 (accepted)

  11. Askin NC, Atis B, Ozturk-Isik E. Accelerated Phosphorus Magnetic Resonance Spectroscopic Imaging Using Compressed Sensing. Proceedings of the IEEE EMBS Annual International Conference. 2012;1: 1106-9.

  12. Askin NC, Demirkan S, Ozturk-Isik E. Partial Saturation Factors and T1 Relaxation Times of 31P MR Spectra of Human Brain at 3T. TMRD 2012. Ankara, Turkey. 24-26 May 2012. (oral presentation)

  13. Demirkan S, Yetimoglu B, Firat Z, Ozturk-Isik E. Estimation of Longitudinal Relaxation Times (T1) of Human Brain Phosphorus Metabolites at 3T. European Society of Magnetic Resonance in Medicine and Biology Annual Conference. Leipzig, Germany, 6-8 October 2011 (oral presentation)

Proton and Carbon MR Spectroscopic Imaging

  1. Li Y, Xu D, Ozturk-Isik E, Lupo JM, Chen AP, Vigneron DB, Nelson SJ. T1 and T2 Metabolite Relaxation Times in Normal Brain at 3T and 7T. Journal of Molecular Imaging Dynamics. 2012. S1:002.

  2. Park I, Chen AP, Zierhut ML, Ozturk-Isik E, Vigneron DB, Nelson SJ. Implementation of 3 T Lactate-Edited 3D (1)H MR Spectroscopic Imaging with Flyback Echo-Planar Readout for Gliomas Patients. Annals of Biomedical Engineering. 2011 Jan; 39(1): 193-204.

  3. Tropp J, Lupo JM, Chen A, Calderon P, McCune D, Grafendorfer T, Ozturk-Isik E, Larson PE, Hu S, Yen YF, Robb F, Bok R, Schulte R, Xu D, Hurd R, Vigneron D, Nelson S. Multi-channel metabolic imaging, with SENSE reconstruction, of hyperpolarized [1-(13)C] pyruvate in a live rat at 3.0 tesla on a clinical MR scanner. Journal of Magnetic Resonance. 2011 Jan;208(1):171-7.

  4. Ozturk-Isik E, Pirzkall A, Lamborn K, Chang SM, Nelson SJ. Spatial Characteristics of Newly Diagnosed Grade 3 Glioma Assessed by Magnetic Resonance Metabolic and Diffusion Tensor Imaging. Translational Oncology. 2012 Feb; 5(1):10-18.

  5. Ozturk-Isik E., Nelson SJ. The Differences of MR Spectroscopic Imaging and MR Diffusion Weighted Imaging Parameters in Different Subtypes of Grade 3 Gliomas. Biyomut 2010. Antalya, Turkey. 21-23 April 2010. (oral presentation)

Tumor Classification Based on Machine Learning

  1. Çıtak Er F, Firat Z, Kovanlikaya I, Ture U, Ozturk-Isik E. Supervised Non-Negative Matrix Factorization Based Classification of Multiparametric MR Imaging of Gliomas at 3T. Submitted to IEEE Journal of Biomedical and Health Informatics, Special Issue on “Bioinformatics in Clinical Environments”. (revised)

  2. Er FC, Firat Z, Sarikaya B, Ture U, Ozturk-Isik E. Supervised Non-Negative Matrix Factorization Based Classification of Multiparametric MR Imaging of Gliomas at 3T. International Society of Magnetic Resonance in Medicine Annual Conference, Milan, Italy, 10-16 May 2014. (e-poster)

  3. Er FC, Vural M, Acar O, Esen T, Onay A, Ozturk-Isik E. Final Gleason Score Prediction Using Discriminant Analysis and Support Vector Machine Based on Preoperative Multiparametric MR Imaging of Prostate Cancer at 3T. International Society of Magnetic Resonance in Medicine Annual Conference, Milan, Italy, 10-16 May 2014. (e-poster)

  4. Çıtak Er F, Firat Z, Kovanlikaya I, Ture U, Ozturk-Isik E. Multivariate Discriminant Analysis of Multiparametric Brain MRI to Differentiate High Grade and Low Grade Gliomas - A Computer-Aided Diagnosis Development Study. Proceedings of the IEEE BIBE Annual International Conference. 2013:1.

  5. Çıtak Er F, Vural M, Acar O, Esen T, Onay A, Ozturk-Isik E. Preliminary Results on Estimation of Final Gleason Score Using Discriminant Analysis on Preoperative Clinical Parameters and Multiparametric MRI Findings in Prostate Cancer. Proceedings of the International Conference on Applied Informatics for Health and Life Sciences. 2013:1.

  6. Çıtak Er F, Fırat Z, Sarıkaya B, Türe U, Öztürk Işık E. Supervised Non-Negative Matrix Factorization-Based Classification of Multiparametric MR Imaging of Gliomas at 3T (Negatifsiz Matris Çarpanlarına Ayırma (NMF) Yönteminin Multiparametrik 3T MR Görüntülerini Kullanarak Gliom Derecesinin Öngörülmesinde Gözetimli Yöntem Olarak Kullanılması). TMRD 2014. Ankara, Turkey. 22-24 May 2014. (oral presentation)

  7. Çıtak Er F, Vural M, Acar O, Esen T, Onay A, Öztürk Işık E. Final Gleason Score Prediction Using Discriminant Analysis and Support Vector Machine Based on Preoperative Multiparametric MR Imaging of Prostate Cancer at 3T (Prostat Kanserinde Gleason Skorunun Multiparametrik 3T MR Görüntüleme ile Ayırma Analizi ve Destek Vektör Makineleri Kullanılarak Öngörülmesi). TMRD 2014. Ankara, Turkey. 22-24 May 2014. (oral presentation)

  8. Er F, Firat Z, Korkmaz EE, Sarsilmaz A, Ture U, Ozturk-Isik E. An investigation of grading of preoperative gliomas based on multiparametric MRI using support vector machine recursive feature elimination and decision tree classification. European Society of Magnetic Resonance in Medicine and Biology Annual Conference. Toulouse, France, 3-5 October 2013 (e-poster)

Other Medical Imaging

  1. Ozturk-Isik E, Cihangiroglu MM, Firat Z, Kilickesmez O, Ulug AM, Ture U. Quantitative Comparison of High and Standard b-Value Diffusion Weighted MR Imaging in Grading Supratentorial Gliomas at 3T. European Society of Magnetic Resonance in Medicine and Biology Annual Conference. Toulouse, France, 3-5 October 2013 (oral presentation)

  2. Aygen B, Fırat Z, Hatay GH, Hamamcı A, Öztürk Işık E. Analysis of Resting State fMRI Data Using Group Independent Component Analysis. (İstirahat Hali (Resting-State) Fonksiyonel Manyetik Rezonans Görüntüleme (RS-fMRG) Verilerinin Grup Bağımsız Bileşen Analizi ile İncelenmesi). TMRD 2014. Ankara, Turkey. 22-24 May 2014. (oral presentation)

  3. Onay A, Vural M, Acar Ö, Esen T, Öztürk Işık E, Gümüş T, Akpek S. Diffusion Tensor Imaging for Prostate Cancer Detection (Difüzyon Tensör Görüntülemenin Prostat Kanserinde Tanısal Değeri). TRD 2013. Antalya, Turkey, 6-10 November 2013. (e-poster presentation)

  4. Kayiş D, Fırat Z, Gürses B, Öztürk Işık E. A Graphical User Interface Design for Magnetic Resonance Spectroscopy of Breast Cancer at 3T. Tıptekno 2013. Antalya, Turkey. 31 October-2 November 2013. (oral presentation)

  5. Şahin E, Fırat Z, Gürses B, Öztürk Işık E. A Graphical User Interface Design for Analyzing T1-Weighted Perfusion Magnetic Resonance Images of Breast Tissue at 3T. Tıptekno 2013. Antalya, Turkey. 31 October-2 November 2013. (oral presentation)

  6. Düzenli İ, Gümüş Ç, Cebeci H, Hakyemez B, Öztürk Işık E. A Graphical User Interface Design for Arterial Spin Labelling Magnetic Resonance Imaging of Brain Tumors at 3T. Tıptekno 2013. Antalya, Turkey. 31 October-2 November 2013. (oral presentation)

  7. Aydın UC, Hatay GH, Firat Z, Askin NC, Ture U, Ozturk-Isik E. Analysis of Speech Function in Brain Tumor Patients by Functional Magnetic Resonance Imaging Using SPM and FSL. TMRD 2013. Ankara, Turkey. 23-25 May 2013. (oral presentation)

  8. Askin NC, Firat Z, Hamamci A, Bilir B, Ture U, Ozturk-Isik E. Analyzing The Activation Points of Hand Movement of Patients Diagnosed With Brain Tumors by Functional Magnetic Resonance Imaging Using SPM. TMRD 2012. Ankara, Turkey. 24-26 May 2012. (oral presentation

  9. Askin NC, Firat Z, Ture U, Kilickesmez O, Ozturk-Isik E. Analyzing The Activation of Accurate Points of Hand Movement of Patients Diagnosed With Brain Tumors by Functional Magnetic Resonance Imaging Technique Using FSL. Biyomut 2011. Antalya, Turkey. 13-16 October 2011. (oral presentation)

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