Radiomics in Lung Cancer from Basic to Advanced: Current Status and Future Directions

Copyright © 2020 The Korean Society of Radiology.Ideally, radiomics features and radiomics signatures can be used as imaging biomarkers for diagnosis, staging, prognosis, and prediction of tumor response. Thus, the number of published radiomics studies is increasing exponentially, leading to a myriad of new radiomics-based evidence for lung cancer. Consequently, it is challenging for radiologists to keep up with the development of radiomics features and their clinical applications. In this article, we review the basics to advanced radiomics in lung cancer to guide young researchers who are eager to start exploring radiomics investigations. In addition, we also include technical issues of radiomics, because knowledge of the technical aspects of radiomics supports a well-informed interpretation of the use of radiomics in lung cancer11Nsciescopuskc

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

nuclear medicine; diagnostic radiolog

Comparison of Texture Features Derived from Static and Respiratory-Gated PET Images in Non-Small Cell Lung Cancer

Background: PET-based texture features have been used to quantify tumor heterogeneity due to their predictive power in treatment outcome. We investigated the sensitivity of texture features to tumor motion by comparing static (3D) and respiratory-gated (4D) PET imaging. Methods: Twenty-six patients (34 lesions) received 3D and 4D [18F]FDG-PET scans before the chemo-radiotherapy. The acquired 4D data were retrospectively binned into five breathing phases to create the 4D image sequence. Texture features, including Maximal correlation coefficient (MCC), Long run low gray (LRLG), Coarseness, Contrast, and Busyness, were computed within the physician-defined tumor volume. The relative difference (δ3D-4D) in each texture between the 3D- and 4D-PET imaging was calculated. Coefficient of variation (CV) was used to determine the variability in the textures between all 4D-PET phases. Correlations between tumor volume, motion amplitude, and δ3D-4D were also assessed. Results: 4D-PET increased LRLG ( = 1%–2%, p0.08) compared to 3D-PET. Nearly negligible variability was found between the 4D phase bins with CV<5% for MCC, LRLG, and Coarseness. For Contrast and Busyness, moderate variability was found with CV = 9% and 10%, respectively. No strong correlation was found between the tumor volume and δ3D-4D for the texture features. Motion amplitude had moderate impact on δ for MCC and Busyness and no impact for LRLG, Coarseness, and Contrast. Conclusions: Significant differences were found in MCC, LRLG, Coarseness, and Busyness between 3D and 4D PET imaging. The variability between phase bins for MCC, LRLG, and Coarseness was negligible, suggesting that similar quantification can be obtained from all phases. Texture features, blurred out by respiratory motion during 3D-PET acquisition, can be better resolved by 4D-PET imaging. 4D-PET textures may have better prognostic value as they are less susceptible to tumor motion

ASSESSMENT OF NEW INNOVATIONS IN PET/CT FOR RESPIRATORY MOTION CORRECTION

In oncological imaging, Positron Emission Tomography/Computed Tomography (PET/CT) is a vital tool used for stating and treatment response assessment of patients due to its ability to visualize and accurately quantify the bio-distribution of radiolabeled pharmaceuticals. However, due to the long acquisition times, respiratory motion blur is unavoidable in PET images especially in the lower lung and upper abdomen. This leads to reductions in measured radiotracer concentration and lesion detectability all of which can potentially result in incorrect management of patients. Multiple methods exist to correct for respiratory motion but are rarely used in the routine clinical setting because of: 1) increased image noise due to the rejection of motion blurred data; 2) burdensome workflows which require setup and troubleshooting of external hardware needed to track patient breathing; 3) and ineffective respiratory motion correction due to irregular patient breathing potentially caused by the abrupt bed transitions during step and shoot (SS) whole body PET acquisition. Our goal of this Ph.D. dissertation is to address these three issues by evaluating 1) a precommercial version of a vendor designed elastic motion correction (EMC) algorithm which uses all of the acquired PET data resulting in reduced image noise; 2) a pre-commercial version of a vendor designed data driven gating (DDG) algorithm, which determines the respiratory waveform from the PET data alone, thereby removing the need for and challenges of external hardware; 3) the effect of using continuous bed motion (CBM) as compared to SS as a means to minimize the irregularity of patient breathing. vii The results of these evaluations showed that the EMC algorithm performed similarly to conventional respiratory motion correction techniques with respect to radiotracer quantification, however, due to using all of the acquired PET data, the EMC algorithm showed improved performance resulting in the lowest amount of image noise, improved contrast to noise ratio, and had the highest overall image quality scores as assessed by independent observers. Evaluation of the CBM DDG algorithm showed that in comparison to an external device, the measured respiratory waveforms, radiotracer quantification, and assessment of the presence of respiratory motion blur were similar, demonstrating that the CBM DDG algorithm holds promise as a replacement to external hardware devices currently needed to measure respiratory waveforms and hence could potentially simplify the data acquisition workflow. Finally, we found no statistically significant differences between the CBM and SS PET acquisition modes with respect to the regularity of respiratory waveforms, radiotracer quantification, contrast to noise ratio and perceptions of respiratory motion blur. In conclusion, although no reductions of irregular breathing were found between CBM and SS, improvements in image quality through the use of EMC and reductions of workflow complexity through the use of DDG will hopefully facilitate the routine adoption of respiratory motion correction in PET/CT

Dual gated PET/CT imaging of heart

Coronary artery disease (CAD) resulting from atherosclerotic arterial changes, plaques, is a progressive process, which can be asymptomatic for many years. Asymptomatic CAD can cause a heart attack that leads to sudden death if the vulnerable coronary plaque ruptures and causes artery occlusion. The plaque inflammation plays an important role in the rupture susceptibility. Reliable anticipation of rupture is still clinically impossible for a single patient. Detection of the vulnerable coronary plaques before clinical signs remains a significant scientific challenge where positron emission tomography (PET) can play an important role. The aim of this dissertation was to find out whether a small, coronary plaque size, heart structures could be detected by a clinically available positron emission tomography and computed tomography (PET/CT) hybrid camera in realistically moving cardiac phantoms, a minipig model, and patients with CAD. Due to cardiac motions accurate detection of small heart structures are known to be problematic in PET imaging. Due to absence of commercial application at the beginning of the study, new dual gating method for cardiac PET imaging was developed and programmed that takes into account both contraction and respiratory induced cardiac motions. Cardiac phantom PET studies showed that small, active and moving plaques can be distinguished from myocardium activity and the gating methods improved the detection sensitivity and resolution of the plaques. In minipig and CAD patient cardiac PET studies small structures of myocardium and coronary arteries was detected more sensitive and accurately when using dual gating method than manufacturer gating methods. In cardiac patient PET study respiratory induced cardiac motions were shown to be linearly dependent with spirometry-measured respiratory volumes. Standard 3-lead electrocardiogram (ECG) measurement can be filtered by anesthesia monitor to detect lung impedance signal. In cardiac patient PET study this lung impedance signal were applied for respiratory gating. In this study was observed that the 3-lead ECG derived impedance signal gating method detects respiratory induced cardiac motion in PET as well as other externally used respiratory gating methods. In summary, the dual gated cardiac PET method is more sensitive and accurate to detect small cardiac structures, as coronary vessel wall pathology, than the commercial methods used in the study.Sydämen kaksoisliiketahdistettu PET/CT kuvantaminen Ateroskleroottisten valtimomuutosten, plakkien, seurauksena asteittain kehittyvä sepelvaltimotauti voi olla vuosia oireeton. Oireeton sepelvaltimotauti voi aiheuttaa äkkikuolemaan johtavan sydäninfarktin, mikäli sepelvaltimon seinämäplakin repeytymisestä aiheutuu verisuonen tukkiva hyytymä. Tutkimuksissa on osoitettu, että plakin tulehduksella on merkittävä rooli repeytymisalttiudelle. Repeytymisen luotettava ennakointi on yksittäisen potilaan kohdalla edelleen kliinisesti mahdotonta. Tulehtuneiden ja repeytymisalttiiden sepelvaltimoplakkien toteaminen ennen kliinisiä oireita on edelleen merkittävä tieteellinen haaste, missä positroniemissiotomografia (PET) kuvantamisella voi olla merkittävä rooli. Väitöskirjan tavoitteena oli selvittää, voidaanko kliinisessä käytössä olevalla positroniemissiotomografia ja tietokonetomografia (PET/TT) yhdistelmäkameralla havaita pieniä, sepelvaltimoplakkien kokoisia, sydämen rakenteita koneellisesti toimivissa todenmukaisissa sydänmalleissa, eläinmallissa ja sepelvaltimotautia sairastavilla potilailla. Sydämen pienten rakenteiden tarkka havaitseminen PET/TTkameroilla on haasteellista sydämen liikkumisen vuoksi. Tutkimuksessa kehitettiin ja ohjelmoitiin uusi sydämen PET-kuvantamisen liiketahdistusmenetelmä, joka ottaa huomioon sekä sydämen supistusliikkeen että hengitysliikkeen vaikutuksen sydämen PET kuvantamissa. Koneellisilla sydänmalleilla osoitettiin, että PET on riittävän herkkä havaitsemaan pieniä ja liikkuvia radioaktiivisia ”sepelvaltimoplakkeja”, ja että liiketahdistusmenetelmät parantavat plakkien havaitsemisherkkyyttä ja tarkkuutta. Eläinmallissa ja sepelvaltimotautipotilailla kaksoisliiketahdistusmenetelmän herkkyys ja tarkkuus havaita pieniä sydänlihaksen ja sepelvaltimoiden rakenteita todettiin kaupallisia tahdistusmenetelmiä paremmaksi. Potilastutkimuksissa todettiin hengityksen aiheuttama sydämen liike PET-kuvissa lineaarisesti riippuvaiseksi spirometrialla mitattujen hengitystilavuuksien kanssa. Tavallisesta 3-johtoisesta sydänsähkökäyrästä voidaan anestesiamonitorin avulla suodattaa keuhkojen impedanssisignaalia. Hengitysliikkeen aiheuttama potilaiden sydämen liike PETkuvissa havaittiin yhtä hyvin käyttämällä tätä keuhkojen impedanssisignaalia kuin muita yleisesti käytettäviä ulkoisia hengitystahdistussignaaleja. Todetaan, että kaksoisliiketahdistettu sydämen PET-kuvantamismenetelmä on tutkimuksessa käytettyjä kaupallisia menetelmiä herkempi ja tarkempi havaitsemaan sydämen pieniä rakenteita sekä sepelvaltimon seinämän tulehdusplakkeja

Respiratory motion correction techniques in positron emission tomography/computed tomography (PET/CT) imaging

The aim of this thesis is to design, implement, and evaluate respiratory motion correction techniques that can overcome respiratory motion artifacts in PET/CT imaging. The thesis is composed of three main sections. The first section introduces a novel approach (free-breathing amplitude gating (FBAG) technique) to correct for respiratory motion artifacts. This approach is based on sorting the acquired PET data in multiple amplitude bins which is currently not possible on any commercial PET/CT scanner. The second section is focused on the hardware/software design of an in-house respiratory gating device that is necessary to facilitate the implementation of the FBAG technique. Currently there are no commercially available respiratory gating systems that can generate the necessary triggers required for the FBAG technique. The third section is focused on developing a joint correction technique that can simultaneously suppress respiratory motion artifacts as well as partial volume effects (PVE) which represent another source of image degradation in PET/CT imaging. Computer simulations, phantom studies, as well as patient studies are conducted to test the performance of these proposed techniques and their results are shown in this thesis

Evaluating and Improving 4D-CT Image Segmentation for Lung Cancer Radiotherapy

Lung cancer is a high-incidence disease with low survival despite surgical advances and concurrent chemo-radiotherapy strategies. Image-guided radiotherapy provides for treatment measures, however, significant challenges exist for imaging, treatment planning, and delivery of radiation due to the influence of respiratory motion. 4D-CT imaging is capable of improving image quality of thoracic target volumes influenced by respiratory motion. 4D-CT-based treatment planning strategies requires highly accurate anatomical segmentation of tumour volumes for radiotherapy treatment plan optimization. Variable segmentation of tumour volumes significantly contributes to uncertainty in radiotherapy planning due to a lack of knowledge regarding the exact shape of the lesion and difficulty in quantifying variability. As image-segmentation is one of the earliest tasks in the radiotherapy process, inherent geometric uncertainties affect subsequent stages, potentially jeopardizing patient outcomes. Thus, this work assesses and suggests strategies for mitigation of segmentation-related geometric uncertainties in 4D-CT-based lung cancer radiotherapy at pre- and post-treatment planning stages

Measurement Variability in Treatment Response Determination for Non-Small Cell Lung Cancer: Improvements using Radiomics

Multimodality imaging measurements of treatment response are critical for clinical practice, oncology trials, and the evaluation of new treatment modalities. The current standard for determining treatment response in non-small cell lung cancer (NSCLC) is based on tumor size using the RECIST criteria. Molecular targeted agents and immunotherapies often cause morphological change without reduction of tumor size. Therefore, it is difficult to evaluate therapeutic response by conventional methods. Radiomics is the study of cancer imaging features that are extracted using machine learning and other semantic features. This method can provide comprehensive information on tumor phenotypes and can be used to assess therapeutic response in this new age of immunotherapy. Delta radiomics, which evaluates the longitudinal changes in radiomics features, shows potential in gauging treatment response in NSCLC. It is well known that quantitative measurement methods may be subject to substantial variability due to differences in technical factors and require standardization. In this review, we describe measurement variability in the evaluation of NSCLC and the emerging role of radiomics. © 2019 Wolters Kluwer Health, Inc. All rights reserved