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QUIBIM at BIO 2017

QUIBIM in BIO 2017

Our company was present again this year in the incredibly huge BIO International Convention in San Diego, California, from June 19th to 22nd. Our registration included both a booth at the Spanish pavilion and the access to the One-to-One partnering meetings.

We had 15 planned meetings and many other new contacts thanks to the interaction at our exhibitor space with agents interested in QUIBIM business model. We made several demonstrations of QUIBIM Precision platform and image analysis capabilities in clinical trials. From all the contacts and meetings performed at BIO, I wanted to point out the classification we found according to their profile:

  • Scientific parks and incubators (30%)
  • Investors in Life Sciences (20%)
  • CRO’s and Pharma companies (50%)

From our experience last year in San Francisco, in this edition there has been a higher interest from scientific parks and incubators beyond Boston and Silicon Valley to attract companies to their facilities, showing the benefits of establishing the companies in specific locations, specially in the different states of US. The number of investors stayed similar, but we have been an increasing interest in the field of Medical Devices. Regarding CRO’s and Pharma companies, most of them are progressively considering medical imaging in their clinical trials, and the best, considering us for their solutions. We are so proud to cover those unmet needs on advanced image analysis services for Clinical Trials, allowing pharma companies, CRO’s and Principal Investigators to follow-up in real time their study. In fact, one of the main trends at BIO this year was how data processing will change the way new drugs are developed and launched into market.

QUIBIM CEO (Angel Alberich-Bayarri) & Booth at BIO 2017

QUIBIM CEO (Angel Alberich-Bayarri) & Booth at BIO 2017

 

We were so glad to have this exhibitor space at the Spanish pavilion, and compared to previous editions, it was also the first time that the Valencia region had a dedicated area inside it (similar to Biocat from Catalonia and Biobasque from Basque Country). The Valencia area was organised by IVACE (Instituto Valenciano para la Competitividad Empresarial), and the organism was represented by Mrs. Mónica Payá (representative for foreign investment of IVACE). The Principe Felipe Research Centre (CIPF), was also represented by Oscar David Sánchez (Projects and Technology Transfer Manager).

Valencia region representatives at BIO 2017 in San Diego, Angel Alberich (QUIBIM), Mónica Payá (IVACE), Daniel Calvo (BIOPOLIS), Marisol Quintero (Biooncotech)

Valencia region representatives at BIO 2017 in San Diego, Angel Alberich (QUIBIM), Mónica Payá (IVACE), Daniel Calvo (BIOPOLIS), Marisol Quintero (Biooncotech)

 

Valencia region representatives at BIO 2017 in San Diego, Óscar David Sánchez (CIPF), Mónica Payá (IVACE), Daniel Calvo (BIOPOLIS), Angel Alberich-Bayarri (QUIBIM)

Valencia region representatives at BIO 2017 in San Diego, Óscar David Sánchez (CIPF), Mónica Payá (IVACE), Daniel Calvo (BIOPOLIS), Angel Alberich-Bayarri (QUIBIM)

 

All the days at BIO were so productive that there is a significant work to be done at home, contacting back with the people we met and following up these new relationships.

Obviously not everything is work and there is also some spare time for entertainment at BIO, in the following picture, a rock band playing at the middle of Gaslamp quarter in San Diego. The streets were closed to welcome BIO 2017 participants in a nice evening with food, drink and music, a nice experience!

Band performing at BIO 2017 in middle of Gaslamp quarter

Band performing at BIO 2017 in middle of Gaslamp quarter

Lymphatic system

Imaging Biomarkers in Lymphoma

Imaging has a crucial role in Lymphoma management nowadays. The main applications are based on the evaluation of disease extension in staging and in treatment response evaluation. Recently, thanks to the technology development of PET-CT and CT scanners, it has shown also a high utility in the evaluation of extra-nodular involvement, the early relapse and the transformation from indolent Lymphoma to an aggressive phenotype [1].

Evidence sets PET-CT and standard CT+contrast as the main imaging modalities for staging and treatment response evaluation. The most suitable modality will depend mainly on the aggressiveness and the FDG avidity of the lesion. Therefore, either for Hodgkin’s Lymphoma (HL), aggressive subtypes of non-Hodgkin’s Lymphoma (NHL) or for extra-nodal involvement evaluation in PET-CT will be the way to go for an appropriate staging. However, in cases of non-FDG avidity, mainly in indolent lymphomas (T-cell lymphoma and subtypes of NHL like Chronic Lymphocytic Leukemia, Marginal Zone Lymphoma, Lymphoplasmacytic Lymphoma), contrast enhanced CT is the main modality. Regarding response evaluation, a similar distribution of lymphoma subtypes per modalities is arrange, with the difference in the Follicular Lymphoma (FL), where PET-CT is the most suitable technique for those FL with a high tumoral burden, whereas low tumoral burden FL should be studied by CT with contrast when studying response. Up to now, Magnetic Resonance Imaging (MRI) has still not shown enough evidence in the management of lymphoma patiens beyond Primary Brain Lymphoma. PET-MR has a promising future in Lymphoma evaluation, specially in the current need for low dose follow-up studies that could be done with this modality.

Imaging Applications in Lymphoma

Imaging Applications in Lymphoma

 

Due to heterogeneities in FDG metabolic uptake in different Lymphoma subtypes, Deauville criteria were established to grade the avidity in comparison with mediastinum and liver. However, conventional PET-CT has limitations in the staging of nodular alterations, with the exception of FL, where PET-CT helps to increase the stage of Lymphoma by detecting additional disease in up to 29% of cases. Regarding response evaluation, PET-CT has been recently considered as the gold standard at end of treatment in FL. This is one of the main conclusions from GALLIUM study.

Despite the previous comments, we understand that the staging and response evaluation in PET-CT in patients under new treatments based on targeted therapies or immunotherapy can not be only based on SUVmax evaluations. New imaging biomarkers have been developed in order to evaluate complex clinical scenarios like indolent Lymphoma or reactive inflammatory changes at the end of treatment in patients that have responded to therapy.

In the following table, specific Imaging Biomarkers for different biological objectives are provided:

Objetive Modality Imaging Biomarker
Tumoral burden PET-CT Metabolic Tumor Volume (MTV)
Tumoral burden + Metabolic activity PET-CT Total Tumor Glycolisis (TTG)
Change in metabolic activity PET-CT Voxelwise Delta-SUV (ΔSUV)
Heterogeneity CT & PET-CT Textures

For Imaging Biomarkers implementation, we always follow the step-wise method that we developed and published and that was also considered in this European Society of Radiology guideline.

The first technical step of Imaging Biomarkers development workflow after an appropriate definition of the idea is the Images Acquisition. In PET-CT, European Association of Nuclear Medicine (EANM) guidelines should be followed, and centres should be ideally certified by EARL program.

Metabolic Tumor Volume (MTV)

The first Imaging Biomarker to be calculated is MTV. It is defined by consensus as those lesion voxels with a significant FDG uptake, that is >41% of SUVmax although different thresholds can be evaluated in practise. The typical units are cm^3. The analysis is performed semi-automatically by thresholding and manual correction.

Calculation of Metabolic Tumor Volume

Calculation of Metabolic Tumor Volume

 

Several studies have analysed MTV values in different types of lymphoma, in the following table from Schöder H. J Clin Onc 2016, a nice summary can be appreciated:

Schöder H, Moskowitz C. Metabolic Tumor Volume in Lymphoma: Hype or Hope? J Clin Oncol. 2016 Sep 6. pii: JCO693747. [Epub ahead of print] PubMed PMID: 27601547.

Schöder H, Moskowitz C. Metabolic Tumor Volume in Lymphoma: Hype or Hope? J
Clin Oncol. 2016 Sep 6. pii: JCO693747. [Epub ahead of print] PubMed PMID:
27601547.

The different thresholds used for MTV can be also appreciated (although 41% SUVmax is the one in the majority of them). Also, the wide range of MTV obtained show us the high heterogeneity of the disease and raises also the concern about treatment dose. Should we modulate the treatment given to patient by the MTV? or, on another way, does a patient with 600cm^3 of MTV have to receive the same treatment dose than a patient with 3000cm^3 ? Important research needs still to be done in this field.

Regarding MTV and Follicular Lymphoma, few studies have been performed. The most important one was a retrospective analysis from Meignan et al, where they calculated a MTV of 510cm^3 for 2-year Progression Free Survival (PFS). However, some controversy has arose mainly due to the fact that the inherent error in SUV measurements due to examination variability introduces a final MTV error in measurements around 20%, so the threshold should not be a single value, but a given range of MTV values that consider that error.

 

Total Tumor Glycolysis (TTG)

The TTG measurements is better applied for specific lesions rather than all lesion burden. Therefore, if we focus on specific lesions, the TTG combines information on the FDG avidity and the MTV of the lesion by the following equation:

TTG = MTV x SUVmean

 

Voxelwise delta-SUV 

The structural and anatomic information contained in the CT examination within the PET-CT acquisition can be used for spatial registration of scans of the same patient corresponding to different timepoints (e.g. registration of end-of-treatment CT on baseline CT). The idea behind this is to create a parametric map of the longitudinal SUV changes in the patient, and for that the deformation field resulting from spatial registration is applied to the end-of-treatment PET in order to convert it to the baseline geometry. After this process, the follow-up examination can be superimposed to the baseline and therefore even substracted to calculate the SUV difference between timepoints.

delta-SUV pipeline

delta-SUV pipeline

 

Textures analysis

The image regions can be also evaluated quantitatively by means of texture analysis. Texture analysis allows for the extraction of quantitative descriptors from voxel intensities relationships within an image or region. They are organised in first order (if directly extracted from histogram) or second order (if an additional step is required for their calculation). Texture analysis and specially heterogeneity biomarkers like the entropy and kurtosis have shown promising results in many different cancerous lesions, specially as a prognostic biomarker.

Texture analysis from lymphoma lesion in CT

Texture analysis from lymphoma lesion in CT

In lymphoma, a recent manuscript from Ganeshan B. et al. has shown excellent results in providing complimentary information to the interim PET as a prognostic biomarker.

However, texture analysis techniques can also be applied to other type of images such as the PET component, being able to determine the metabolic heterogeneity (MH) of the lesions. In this regard, lesions with different regional FDG avidity are having a worse prognosis than lesions with a homogeneous FDG uptake.

Metabolic Heterogeneity in FDG uptake in lymphoma

Metabolic Heterogeneity in FDG uptake in lymphoma

 

As you have discovered in this post, there are still many Quantitative Imaging Biomarkers that can be extracted from conventional FDG PET-CT examinations, and which are showing important relationship with lymphoma progression, according to recent investigations. In QUIBIM we are a committed team dedicated to the implementation of these techniques in clinical practise, research and clinical trials. If you want to collaborate with us in this field do not hesitate to contact us and potentially upload a case through our QUIBIM Precision® platform. It will be the best way to start working together in this emerging field.

 

 

3D_Full_Low_Both

Assessing the bone quality of your patients is just a few clicks away

Quibim is proud to introduce its new advanced methodolgy to assess bone quality and fracture risk: QTS (Quality of Trabecular Structure). The need for a reliable approach for the characterization of trabecular microarchitecture is evident, as conditions and diseases related to trabecular bone quality and structure are becoming a focal point of precision medicine. Millions of dollars are spent in bone fracture care and prevention, which in many cases represent a grave danger to the patient health. In this scenario, can we rely upon available methods to predict bone fractures? Regrettably, the answer is no. Or so it was. Before we introduce QTS in detail, let’s first review some of the available methods to evaluate fracture risk.

DEXA Bone Mineral Density (BMD) limitations as a fracture predictor are widely known. However, despite its glaring shortcomings it’s still considered as the gold standard in clinical practice. The WHO developed the FRAX tool hoping to improve the low ratio of success of BMD as a predictor, and, while it improves sensibility and specificity assessing fracture risk, it’s still not satisfactory enough for it to be used as a stand-alone predictor in clinical practice or clinical trials.

In an attempt to fill this void in the search of a reliable predictor, new imaging biomarkers that guarantee to provide the needed sensibility and specificity have been developed. Trabecular Bone Score (TBS®) by Medimaps is a fracture risk predictor using DEXA as a source. TBS® performs a gray level analysis (textures) on the DEXA images to determine bone integrity. But, is DEXA adequate for this task? Unlike regular XR, in which it’s possible to assess the trabecular structure, DEXA’s low radiation is not enough for trabeculae differentiation. In addition, DEXA (like XR) represents a 3D structure as a projection onto a plane, losing spatial information.

Other medical imaging modalities are much more adequate for bone analysis and the subsequent fracture risk evaluation. Thanks to advanced computing models, Quibim has developed a new imaging biomarker that uses either magnetic resonance (MR), computerized tomography (CT) or X-ray imaging for a detailed characterization of the trabecular structure. QTS (Quality of Trabecular Structure) by Quibim introduces several advantages over other analysis methods:

  • Real extraction of the trabecular bone microarchitecture: bone volume, trabecular thickness, trabecular separation…
  • Information of the complexity of the structure: fractal analysis
  • 3D spatial information, not only in plane (only CT and MR)
  • 3D reconstruction of the trabecular bone (only CT and MR)
  • Optional mechanical analysis (only CT and MR, with QTS+)
  • QTS Score comprises all this information in a single score for a rapid and accurate characterization of the bone structure.

This groundbreaking analysis method is already available at our cloud web platform: Quibim Precision. Below we detail how to analyze your study in a few simple steps.

Quibim Precision allows the upload of studies in Dicom format. The upload process is easy, intuitive and 100% secure, guaranteeing the patient confidentiality thanks to Quibim’s anonymization and encryption system. The whole process is performed without the need of installing any additional software. To start, click on the green “Upload Study” button to the right of the website.

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The platform will then ask for Dicom studies selection. With Google Chrome, we can drag and drop the study folder directly to the dotted box. With any other browser, we need to select the Dicom files to be uploaded.

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Once the Dicom folders have been selected, Quibim Precision allows the pre-visualization of the study to choose which sequences we wish to upload. In this case, we need a CT, an X-ray or a 3D T1 MR.

After the selection, the files will be anonymized and encrypted. Quibim Precision will ask for an encryption password before the upload process starts. The user needs to preserve this password, as it’s needed for patient traceability.

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After the upload process is completed, we click on the “Analyze Study” button of the study we want to evaluate.

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This will take us to the detailed view of the study, where we can perform all actions related to it. First of all, we will choose among all the available sequences the one to be analyzed and its Quibim standard name. In this case, the name of the sequence is “Linear Attenuation [1/cm] (3035)”, which corresponds to the standard name “High Resolution CT”.

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Next, we open the embedded Dicom viewer by clicking on “View”. Thanks to this viewer we can draw the ROI that will be used for the analysis. The viewer allows drawing 3D ROIs, first drawing a 2D rectangular ROI, and then selecting the slices on which it should be replicated. Clicking on “Apply” and “Save and go back” will store the ROI and it will be used for the analysis.

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Finally, we should choose which analysis method we’ll use among all the available apps in Quibim Precision. In this case we’ll click on the “Start Analysis” button of the “3D Bone microarchitecture – QTS Score” app. The analysis process will then start, and the user doesn’t need to perform any other action than checking the results.

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The results of the analysis are available on the view of the study. Once the analysis is completed we can check them by clicking on the “View Study” button on the “Processed Biomarkers” section.

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We can examine the 3D reconstruction images and the numeric results of the extracted imaging biomarkers on the results view. Furthermore, we can download them and the structured report in pdf format, which includes all the generated data in a compact, easy to read way.

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All the benefits of QTS are just a few clicks away. Create an account on Quibim Precision and start offering a real added value with your imaging studies.

Try us for free!

Have you seen the QUIBIM video teaser?

QUIBIM has launched a new video describing the advanced Imaging Biomarkers analysis process performed at our company. From the assistance and consultancy in medical images acquisition (MR, CT, PET, US, X-Ray, …), through image processing and quantification, to the final structured report generation containing the most relevant information for the clinician, researcher or clinical trials CRO companies.