tumor – QUIBIM

QUIBIM to develop platform in leading research project to fight pediatric cancer

26 June, 2019

QUIBIM is helping to advance knowledge of the most lethal pediatric tumors through EU-funded program PRIMAGE, which exploits precision information from medical imaging to establish tumor prognosis, and expected treatment response using radiomics, imaging biomarkers and artificial intelligence (AI).

Pediatric cancer is a rare disease, but treatment remains challenging. Improving knowledge is key to adequately plan therapy and boost survival, and the latest AI techniques have the potential to harness unprecedented information from medical images.

A few months ago, the European Commission funded the PRIMAGE (1) project with over €10M, to help identify the most efficient treatment and a tumor’s main characteristics without the need for biopsy, by using computational processing of medical images on the cloud.

The PRIMAGE consortium will create a bank of images obtained through AI, using an open cloud-based platform to support decision-making in the clinical management of Neuroblastoma (NB), the most frequent solid cancer of early childhood, and Diffuse Intrinsic Pontine Glioma (DIPG), the leading cause of brain tumor-related death in children. The PRIMAGE platform will implement the latest advancement of in-silico imaging biomarkers and modeling of tumor growth towards a personalized diagnosis, prognosis and therapies follow-up.
The project involves 16 European partners, including internationally recognized institutions, and four leading industrial partners, including Spanish biotechnology company QUIBIM, all working under the aegis of the Imaging Biomedical Research Group (GIBI230) based in La Fe Hospital, Valencia.

Sharing high-end knowledge of AI tools

QUIBIM is responsible for the central task of developing the PRIMAGE platform’s architecture, adaptation and design. The company recently obtained CE mark for its Chest X-Ray Classification AI-Tool and its imaging biomarker analysis algorithms, zero footprint DICOM viewer and platform within the QUIBIM Precision platform.

QUIBIM researchers are now bringing their expertise in medical image post processing and management to PRIMAGE, by passing on their knowledge of clinical trials design and validation, imaging biomarkers extraction and validation, radiomics, data clustering and visualization, and development of AI-fueled tools, such as organ segmentation models.
“Much work remains to be done to improve our knowledge of pediatric brain cancer. NB and DIPG have a complex therapeutic approach and we need proper tools to improve survival. Extracting quantitative information from medical images with AI can help visualize tumor growth with extreme precision, and help to tailor therapy to each individual patient,” Ángel Alberich-Bayarri said.

QUIBIM’s input will also help to define the methodologies and standards to be used in the different development areas, to facilitate interoperability between the platform ́s modules and for future interoperability with their cloud-based platforms for functionality add-ons.

Transferrable knowledge to other cancers

Cancer has a very low incidence among children and experts estimate that 500,000 EU citizens will be pediatric cancer survivors by 2020. Nonetheless, cancer remains the first cause of non-traumatic death among children.

Neuroblastoma is the most common extracraneal tumor in children, representing 8-10% of all pediatric cancers. In Europe, 35,000 new cases are diagnosed each year, 1,000 in Spain alone.

Diffuse Intrinsic Pontine Glioma is a very rare disease in childhood and is associated with low survival (10%), despite many existing treatments and on-going research. Treatment is not curative, only palliative, i.e. radiotherapy to improve the patient’s life. 16 new cases are diagnosed each year in Spain, accounting for 2.5% of oncological pediatric patients and 13% of pediatric tumors of the central nervous system.

Because of the peculiarities of computational approximation in these two types of tumors that are proper to childhood, investigation done in that area will also be applicable to other types of tumors. Because it will gather considerable scientific effort, PRIMAGE should also help advance research on other types of cancer.
(1): PRedictive In-silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers (PRIMAGE)

QUIBIM now offering advanced MR spectroscopy analysis including 2-HG for IDH1 mutation detection

By: Paula Moreno

4 March, 2019

Continuing its focus in the field of Oncology, QUIBIM is proud to offer an advanced MR Spectroscopy analysis tool. This tool developed in house by QUIBIM will help oncologists to improve diagnosis and treatment of brain gliomas, a disease that has an incidence of 22.6 per 100.000 population in United States.

In order to have reproducible, reliable and accurate information from tumors, we provide physicians with quantification of the metabolite by analyzing Magnetic Resonance Spectroscopy (MRS) images. MRS is a non-invasive imaging technique widely used to obtain chemical information by detecting relevant metabolites concentration from a spectrum.

Even though it is possible to detect almost any metabolite in the body, QUIBIM is currently focusing on the detection of the 2-Hydroxyglurate (2HG) because of its influence in the prediction of low-grade brain gliomas. 2HG is a metabolite, normally present at very low levels in healthy cells and tissues because of the reduction of α-ketoglutarate (α-KG) catalyzed by isocitrate dehydrogenase (IDH) protein. The IDH enzyme mutation in low-grade brain gliomas produces an accumulation of 2-HG which makes the measurement of this oncometabolite crucial to distinguish IDH-mutant gliomas from other brain mass (Stefan, et al., 2010).

MRI quality assurance

The quality assurance of the Magnetic Resonance Imaging (MRI) images is important and mandatory to ensure consequent and reliable results from the MR analysis. For that reason, a qualitative evaluation of the images is performed by QUIBIM to guarantee a strict and standard control of the images by checking the accomplishment of the MRI acquisition protocol set and the absence of artifacts.

MRS quality assurance

The first technical information QUIBIM provides with, is the graphical representation of the voxel placement in the sagittal, axial and coronal view depicted in a structural image. This quality review is important in order to assure the correct position of the voxel in the MRS acquisition avoiding necrotic tissue or non-tumor substances what can affect MRS results.

MRS quantification

Once the quality check of the MRS acquisition is done, QUIBIM produces a technical structured report, quantitative and graphical information about the MRS analysis.

The report, apart from the main images and quantitative information, includes a spectrum graph and the voxel placement. Each peak of the spectrum corresponds to a different substance or metabolite with a different resonance frequency. This difference is usually measured in an independent scale besides the principal magnetic field (parts per million). The intensity of each peak is related to the concentration of the substances in the studied volume (Sánchez, et al., 2001).

To perform the analysis, the voxel in the tumor area and a reference acquisition corresponding to water are required. An automatic analysis of the spectrum is done providing this information and setting the up and down boundary value in ppm according to the metabolite searched. Then, we automatically process the spectrum filtering the water peak in the time domain, reducing the spectrum noise, adjusting the ppm scale according to Creatine and Choline position, and correcting the phase of the signal in order to also correct the baseline offset level to ensure the reliability and accuracy of metabolites’ concentration (Martí-Bonmatí & Alberich-Bayarri, 2013).

Therefore, it is possible to obtain from the studied metabolite its absolute concentration, the percentage of standard deviation (%SD) and its relative concentration using Creatine as a reference value (/Cr), sometimes adding other reference metabolites like PCr as the example of Figure 1 (/Cr+PCr).

The information provided by the standard deviation is essential to read MRS results because absolute concentration reliability depends on them: metabolites with a %SD less than 50 are practically undetectable with this data whereas a %SD<20 is a rough criterion for estimates of acceptable reliability. In addition, the third column indicates ratio relative to /Cr. This quantitative information will appear in the lower part of the report followed by a space for the signature of the scientist from QUIBIM once the analysis is done.

MRS analysis is now available in QUIBIM Precision® Platform to support oncologists and radiologists in brain gliomas treatment and diagnosis.

References

Francesca Branzoli, *. A. (2018). Highly specific determination of IDH status using edited in vivo magnetic resonance spectroscopy. Neuro-Oncology, 907-916.
Martí-Bonmatí, L., & Alberich-Bayarri, Á. (2013). Disease Biomarkers: Modelling MR Spectroscopy and Clinical Applications in Bioinformatics of Human Proteomics. Valencia: Springer.
Min Zhou, *. Y. (2018). Diagnostic accuracy of 2-hydroxyglutarate magnetic resonance spectroscopy in newly diagnosed brain mass and suspected recurrent gliomas. Neuro-Oncology, 1262-1271.
Sánchez, J., Santos, A., SantaMarta, C., Benito, C., Benito, M., & Desco, M. (2001). Herramienta de Análisis de Espectros de RM. CASEIB. Madrid.
Stefan, G., Rob A., C., Mark D., M., Edward M., D., Mark A., B., Hyun Gyung, J., . . . David P., S. (2010). Cancer-associated metabolite 2-hydroxyglutarate accumulates in acute myelogenous leukemia with isocitrate dehydrogenase 1 and 2 mutations. Journal of experimental Medicine, 207(2), 339–344.