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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:

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.



Quibim Team

We are Hiring! Do you want to be a Quibimer?

We are excited to announce that we are seeking an Engineer to join our fantastic team in Valencia.

What do we need?

  • Enginner with 1-2 years of experience in the field of software development and medical imaging (biomedical, Computing, Electronics)
  • Experience as Java Developer
  • Experience with SQL databases
  • Experience in web development based on API-REST
  • Experience with GIT version control
  • Experience in application deployment with Apache Tomcat
  • Fluent english

Our ideal candidate’ Skills & Experience…

  • Experience with Spring or Jersey frames
  • Experience in integrating external APIs
  • Experience with the dcm4che library
  • Test Driven Development Experience (TDD / BDD)
  • Experience with the DICOM and HL7 standards
  • Experience in integration with PACS and RIS systems
  • Experience in developing CLI applications

What is a plus?

  • Experience with the C ++, Python or NodeJS languages
  • Experience as a FrontEnd
  • Experience with NoSQL databases
  • Experience with Microsoft Azure

If you are proactive, dynamic and forward thinking profile Apply Here



La empresa QUIBIM S.L y la Fundación IVI han firmado un acuerdo de colaboración para el desarrollo de un proyecto científico en el ámbito de las enfermedades ginecológicas y/o reproductivas.

El proyecto está coordinado por el Profesor José Remohí, Presidente y Fundador de IVI, como Investigador Responsable, y por el Dr. Ángel Alberich, como fundador y director de QUIBIM SL, empresa spin-off del Instituto de Investigación Sanitaria La Fe dedicada al análisis avanzado de imágenes médicas.

Este acuerdo tiene como objetivo utilizar la tecnología de detección basada en algoritmos computacionales de imagen médica desarrollados por QUIBIM para la evaluación de la tasa de éxito en la donación de óvulos. El principal objetivo del proyecto es la aplicación de biomarcadores de imagen extraídos a partir de imágenes ecográficas para caracterizar la receptividad endometrial, ya que según la experiencia de los miembros del acuerdo el estado de esta membrana es un factor clave en la reproducción humana y fundamental en el tratamiento de donación de óvulos.

En el caso de pacientes sometidas a técnicas de reproducción asistida es preciso establecer y caracterizar los factores que contribuyen a aumentar la tasa de éxito en la implantación del embrión en el endometrio, para disponer de criterios objetivos sobre la posibilidad de embarazo.

El proyecto desarrollado por las dos empresas valencianas se hace con la finalidad de esclarecer unos métodos de diagnóstico y pronóstico en el área ginecológica y de la reproducción asistida.

Ángel Alberich Bayarri, ha destacado que “este acuerdo nos permite avanzar en un terreno hasta ahora desconocido en la medicina reproductiva como es la extracción de biomarcadores de imagen a partir de imágenes ginecológicas con la filosofía point-of-care, es decir, en la propia consulta. Con este proyecto buscamos biomarcadores pronósticos, y sus resultados pueden supones un cambio de paradigma en el manejo de las imágenes ginecológicas en la práctica clínica”.

Por su parte el Profesor Remohí ha asegurado que “para IVI la investigación siempre ha formado parte de la base de nuestra empresa. Es uno de nuestros pilares y este convenio nos va a permitir seguir trabajando en un proyecto científico en el ámbito de las enfermedades ginecológicas y reproductivas”.


QUIBIM es una empresa biotecnológica de análisis avanzado de imágenes médicas, fue una de las start-ups valencianas seleccionadas en la 3ª edición del programa Lanzadera, actual Spin-off del programa Biopolo La Fe del Instituto de Investigación Sanitaria La Fe y que recientemente he cerrado una ronda de inversión para impulsar su crecimiento. El modelo de negocio de QUIBIM (Quantitative Imaging Biomarkers in Medicine) se basa en la extracción de información cuantitativa de las imágenes médicas radiológicas y de medicina nuclear mediante técnicas originales y avanzadas de procesamiento computacional.

Sobre FIVI

La Fundación IVI, tiene como objetivo fundamental la Investigación básica y aplicada, la Docencia y la Responsabilidad Social Corporativa en el campo de la Reproducción Humana. La Fundación IVI opera como entidad sin ánimo de lucro y con autonomía funcional, con la finalidad de prestar un servicio de carácter científico, docente y social desde su fundación en el año 1997.

La Fundación IVI vehiculiza la producción científica y docente del grupo IVI y cuenta con más de 600 personas con perfil docente e investigador.


Quibim Precision V2.0

It is a real pleasure for Quibim to announce the release of Precision 2.0. On this new version, we have focused on improving its performance, making it more powerful and user friendly. Keep reading to know how we did it…
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QUIBIM recibe la ayuda AVALEM Joves de la Generalitat

QUIBIM ha recibido una subvención de 9.172,80 € ( Nº de expediente: ECOGJU/2016/53/46) para la contratación de jóvenes cualificados en el marco del Sistema Nacional de Garantía Juvenil.

La ayuda AVALEM Joves se encuentra bajo el Plan integral de formación y empleo para jóvenes cualificados 2016-2020, y esta cofinanciada por el Fondo Social Europeo y la Iniciativa de empleo juvenil de la Generalitat.

Gracias a esta subvención nuestro equipo incorpora un nuevo miembro, Katherine Wilisch, licenciada en biotecnología y con amplios conocimientos como social media manager y marketing digital, con el objetivo de dinamizar nuestros servicios de diagnóstico y análisis avanzado de imagen médica y dar a conocer nuestra plataforma de análisis QUIBIM Precision® de análisis de Biomarcadores de Imagen a nivel internacional.

Visit of the group of Dr. Regina Beets-Tan and Dr. Erik Ranschaert to QUIBIM headquarters

The satisfaction of bringing together the best experts in the world at home

Dr. Luis Martí-Bonmatí (QUIBIM co-founder and director of advisory board) and myself had been locally organising the joint congress of the European Society of Oncological Imaging (ESOI) and the European Society of Medical Imaging Informatics (EuSoMII) for approximately 1 year, and the event finally took place past October from 6th to 8th at our home. The Venue was our hospital: La Fe Polytechnics and University Hospital, where we develop our professional activity and where QUIBIM headquarters are placed, since QUIBIM is a spin-off Company of La Fe Health Research Institute, the institutional arm of the hospital to perform research.

The topic of the congress was “Imaging Informatics in Oncology” and it was the result of joining both Societies fields like Oncology and Medical Imaging Informatics from ESOI and EUSOMII, respectively. The congress program combined workshops with plenary sessions. The workshops covered different concrete areas like Response to treatment, Tumor Boards, 3D printing, and Imaging Informatics for clinicians and computer scientists. The complete program can be found here.

I had the opportunity to present on our stepwise development of Imaging Biomarkers process and the associated bottlenecks for validation. Here you can find the slides of the presentation.

Our group had a really active participation, either from the Biomedical Imaging Research Group (GIBI230) from our Hospital and from QUIBIM.

The main scientific presentations were:

  1. ProstateChecker, a tool for the multi-variate analysis of Prostate Cancer from T2, diffusion and perfusion MR sequences, by David García-Juan, post-processing biomedical engineer at QUIBIM
  2. Cloud architecture for Imaging Biomarkers analysis, by Rafael Hernández, CTO at QUIBIM
  3. Spatial registration on PET-CT scans and quantitative structured report for treatment response evaluation on lymphoma patients, by Fabio García-Castro, post-processing biomedical engineer at QUIBIM
  4. Web application for PI-RADS 2.0 Structured Reporting, by Enrique Ruiz-Martínez, CTO at GIBI230 group
  5. Business analytic, metric, key performance indicator. Automating the monitorization of performance indicators in Radiology departments, by Enrique Ruiz-Martinez, CTO at GIBI230 group
  6. Platform for the integration of Imaging Biomarkers in Radiology Departments, by Enrique Ruiz-Martinez, CTO at GIBI230 group
  7. Integration of Redmine as a tool to manage Clinical Trials in Radiology, by Amadeo Ten-Esteve, Clinical Trial Manager at GIBI230 group.
  8. Artificial intelligence techniques applied to medical imaging. Deep learning applied to automated chest X-ray screening, by Belén Fos-Guarinos, internship biomedical engineering student at GIBI230 group.
  9. Automatic vertebrae localization in pathological spine CT using Decision Forests, by Ana Jiménez Pastor, internship telecommunications engineering student at QUIBIM.
  10. Automated segmentation of muscle using Neural Networks, by Sara Rocher, internship biomedical engineering student at GIBI230 group.
  11. Automatic classification of intensity-vs-time curves in breast DCE-MRI by K-means clustering and Dynamic Time Warping curve matching, by Fabio García-Castro, post-processing biomedical engineer at QUIBIM

In the meantime, the QUIBIM stand was boiling! With several experts interested…

QUIBIM CEO, Angel Alberich-Bayarri explaining QUIBIM advantages to interested attendees to EUSOMII - ESOI congress

QUIBIM CEO, Angel Alberich-Bayarri explaining QUIBIM advantages to interested attendees to EUSOMII – ESOI congress

Besides the opportunity to present the work of our group, we had some remarkable visits to our headquarters, like the visit of Dr. Regina Beets-Tan group together with Dr. Erik Ranschaert (see photo).

Visit of the group of Dr. Regina Beets-Tan and Dr. Erik Ranschaert to QUIBIM headquarters

Visit of the group of Dr. Regina Beets-Tan and Dr. Erik Ranschaert to QUIBIM headquarters

Industry also visited us, in this case it was Agfa Healthcare. The Global Senior Solution Manager, Mr. Chris Townend and the National Sales Manager, José Vicente Puig visited our headquarters and attended the demo of our solution.

Visit of José Vicente Puig (National Sales Manager at Agfa Healthcare) and Chris Townend (Global Senior Solution Manager at Agfa Healthcare)

Visit of José Vicente Puig (National Sales Manager at Agfa Healthcare) and Chris Townend (Global Senior Solution Manager at Agfa Healthcare)


The last day we were lucky to have Regina Beets-Tan and Sergey Mozorov, new presidents of ESOI and EUSOMII, respectively, at our headquarters.


Visit of Sergey Morozov and Regina Beets-Tan. Photo with QUIBIM founders

Visit of Sergey Morozov and Regina Beets-Tan. Photo with QUIBIM founders


The experience speaks by itself.

Katherine Wilisch new member of QUIBIM team

A new ‘quibimer’ in our team

We are pleased to announce the incorporation of Mrs. Katherine Wilisch Ramírez as a new member of our team. Katherine is graduate in Biotechnology and Master in Human Genetics by the University of Valencia has recently joined to the QUIBIM team as General Coordination and CEO support. Katherine has a remarkable experience in the field of innovation and technology transfer. She previously was coordinator at the VIT salud network and at the Spanish Association of Scientific Entrepreneurs. She has collaborated in the organisation of more than 10 events related to health, technology and innovation. We welcome Katherine in our team and we wish her a brilliant future in QUIBIM. Enjoy this new experience of your life joining our great team and thank you for becoming a ‘quibimer’.

Katherine Wilisch new member of QUIBIM team

Katherine Wilisch new member of QUIBIM team

Our experience at BIO 2016 and USA tour

We were delighted to be present at past BIO conference in San Francisco (Moscone Center), from 6th to 9th of June, with a booth in the Spanish pavillion. Our presence was due to the incorporation of QUIBIM in the ICEX next program, the Spanish program that assists SME’s in their internationalization.

I can now confirm that the meeting covered my expectations and I agree with the definition in their website: The BIO International Convention (BIO) attracts over 15,000 biotechnology and pharma leaders who come together for one week of intensive networking to discover new opportunities and promising partnerships. This event covers a wide spectrum of life science and application areas including drug discovery, biomanufacturing, genomics, biofuels, nanotechnology and cell therapy.

QUIBIM stand at BIO convention in Spain Pavillion and its CEO, Angel Alberich-BayarriQUIBIM stand at BIO convention in Spain Pavillion and its CEO, Angel Alberich-Bayarri

The attendees were also variate:

  • One-third of BIO attendees come from outside the U.S.
  • 2,500+ CEO’s from leading biotech companies
  • More than 70% of attendees are either Managers, Directors, C-Level or Executive Management.
  • All company sizes: 33% of attendees are from companies with more than 500 employees and 40% are from companies with fewer than 50 employees.

Our first event in the congress was the session “Spain Kicks off 2016 BIO International Convention” in a charming venue: The Ferry Building. A session were we were able to learn from leading experts on how to select the appropriate path, develop and execute our strategy successfully, as well as best practices and what we need to understand in any approach. High level executives from TTS Global Initiative, Breakout Labs, CytomX, GeronIRB Barcelona, pH PharmaRoche, Stanford University and the Thiel Foundation participated in the panel.

In the BIO convention, we had a total of 23 one-to-one partnering meetings organised. The meetings were very well organised and distributed and having the possibility of discussing 30 minutes with potential customers, providers or investors to explore further ways of collaboration justifies our presence in the congress. New business opportunities that are now being executed arose.

After BIO convention, we decided to spend a pair of days at Case Western Reserve Medical Center in Cleveland, visiting Dr. Pablo Ros, member of our advisory board and Chairman at the Department of Radiology in UH Case Medical Center. The purpose of the visit was to discover the biomedical engineering department and the projects that are being performed. Among the short meetings I shared with senior reserchers, I must highlight the meeting with Dr. Mark Griswold, the promoter of the MRI fingerprinting technique.

In summary, we will probably repeat our attendance at BIO conference due to the success of networking.


QUIBIM awarded with Phase I of SME Instrument Program 2016 H2020 by the European Commission  

QUIBIM is one of the disruptive companies selected by the EU to be granted with the first round of Horizon 2020 SME Instrument Phase I Program 2016 under the call: “SMEInst-01-2016-2017: Open Disruptive Innovation Scheme”. A H2020 funding-call with a success rate of 10%.

The dedicated SME instrument supports close-to-market activities, with the aim to give a strong boost to breakthrough innovation. Highly innovative SMEs with a clear commercial ambition and a potential for high growth and internationalization are the prime target.

The European Commission will support QUIBIM project either economically and with a coaching program, helping it grow and expand as an international core reference laboratory for image centralization and medical image processing.

QUIBIM team is really proud of being elected by the EU with its first submitted proposal and we are really grateful for this relevant acknowledgment. We are already working on phase I, exploring and assessing the commercial potential of our innovative medical imaging services.

QUIBIM ha sido seleccionada por la Comisión Europea para la Fase I del Programa Instrumento PYME 2016 del H2020

QUIBIM ha sido una de las empresas seleccionadas por la CE en la primera convocatoria de Fase I del Programa Instrumento PYME 2016 del H2020 bajo la llamada: “SMEInst-01-2016-2017: Open Disruptive Innovation Scheme”. Un Programa del H2020 con una tasa de éxito del 10%.

El Instrumento PYME es una inicitativa dedicada al apoyo de actividades cercanas a mercado con el objetivo de impulsar la innovación disruptiva. PYMEs altamente innovadoras, con una ambición comercial clara y alto potencial de crecimiento e internacionalización son las candidatas a ser subvencionadas por este Programa.

La Comisión Europea apoyará el proyecto QUIBIM tanto económicamente como con ‘coaching’ internacional, impulsando así el crecimiento y la expansion de la empresa como laboratorio internacional de referencia para la centralización y el procesamiento de imágenes médicas.

En el equipo QUIBIM estamos muy orgullosos de haber sido elegidos por la CE en nuestra primera propuesta presentada y agradecidos por este importante reconocimiento. Actualmente, nos encontramos ya trabajando en esta Fase I, inmersos en la exploración y la evaluación del potencial comercial de nuestros servicios disruptivos en imagen médica.


Let’s meet at the ESOI and EuSoMII Annual Meeting 2016

ESOI and EuSoMII will organise this year’s annual meeting jointly. The meeting will give imaging doctors the opportunity to understand the importance of informatics for oncologic imaging, in both clinical practice and research. It will also give insight on how information technology may contribute to enhance the multidisciplinary management of cancer patients and improve communication. A comprehensive series of workshops will be offered to participants, tailored for both clinicians and computer scientists. These courses will give the unique opportunity to discuss clinical cases in a multidisciplinary setting, train on specialized software and test structured reporting solutions.

The meeting, co-organized by QUIBIM founders, will take place in beautiful Valencia, a culturally rich and diversified city, an open-air museum overlooking the Mediterranean Sea.
We look forward to welcoming you in Valencia!

Congress Registration:
Click here to secure your place for the ESOI/EuSoMII Congress.

Congress Venue
Hospital La Fe
Avinguda de Fernando Abril Martorell, nº 106
46026, Valencia

Congress Programme
Kindly find the detailed preliminary programme on the ESOI website.