Analytical performance validation of aPROMISE platform for prostate tumor burden, index and dominant tumor assessment with 18F-DCFPyL PET/CT. A pilot study.

To validate the performance of automated Prostate Cancer Molecular Imaging Standardized Evaluation (aPROMISE) in quantifying total prostate disease burden with 18F-DCFPyL PET/CT and to evaluate the interobserver and histopathologic concordance in the establishment of dominant and index tumor. Patients with a recent diagnosis of intermediate/high-risk prostate cancer underwent 18F-DCFPyL-PET/CT for staging purpose. In positive-18F-DCFPyL-PET/CT scans, automated prostate tumor segmentation was performed using aPROMISE software and compared to an in-house semiautomatic-manual guided segmentation procedure. SUV and volume related variables were obtained with two softwares. A blinded evaluation of dominant tumor (DT) and index tumor (IT) location was assessed by both groups of observers. In histopathological analysis, Gleason, International Society of Urological Pathology (ISUP) group, DT and IT location were obtained. We compared all the obtained variables by both software packages using intraclass correlation coefficient (ICC) and Cohen's kappa coefficient (k) for the concordance analysis. Fifty-four patients with a positive 18F-DCFPyL PET/CT were evaluated. The ICC for the SUVmax, SUVpeak, SUVmean, tumor volume (TV) and total lesion activity (TLA) was: 1, 0.833, 0.615, 0.494 and 0.950, respectively (p < 0.001 in all cases). For DT and IT detection, a high agreement was observed between both softwares (k = 0.733; p < 0.001 and k = 0.812; p < 0.001, respectively) although the concordances with histopathology were moderate (p < 0001). The analytical validation of aPROMISE showed a good performance for the SUVmax, TLA, DT and IT definition in comparison to our in-house method, although the concordance was moderate with histopathology for DT and IT.

Freely Available, Fully Automated AI-Based Analysis of Primary Tumour and Metastases of Prostate Cancer in Whole-Body [18F]-PSMA-1007 PET-CT.

Here, we aimed to develop and validate a fully automated artificial intelligence (AI)-based method for the detection and quantification of suspected prostate tumour/local recurrence, lymph node metastases, and bone metastases from [18F]PSMA-1007 positron emission tomography-computed tomography (PET-CT) images. Images from 660 patients were included. Segmentations by one expert reader were ground truth. A convolutional neural network (CNN) was developed and trained on a training set, and the performance was tested on a separate test set of 120 patients. The AI method was compared with manual segmentations performed by several nuclear medicine physicians. Assessment of tumour burden (total lesion volume (TLV) and total lesion uptake (TLU)) was performed. The sensitivity of the AI method was, on average, 79% for detecting prostate tumour/recurrence, 79% for lymph node metastases, and 62% for bone metastases. On average, nuclear medicine physicians' corresponding sensitivities were 78%, 78%, and 59%, respectively. The correlations of TLV and TLU between AI and nuclear medicine physicians were all statistically significant and ranged from R = 0.53 to R = 0.83. In conclusion, the development of an AI-based method for prostate cancer detection with sensitivity on par with nuclear medicine physicians was possible. The developed AI tool is freely available for researchers.

Automated classification of PET-CT lesions in lung cancer: An independent validation study.

INTRODUCTION: Recently, a tool called the positron emission tomography (PET)-assisted reporting system (PARS) was developed and presented to classify lesions in PET/computed tomography (CT) studies in patients with lung cancer or lymphoma. The aim of this study was to validate PARS with an independent group of lung-cancer patients using manual lesion segmentations as a reference standard, as well as to evaluate the association between PARS-based measurements and overall survival (OS). METHODS: This study retrospectively included 115 patients who had undergone clinically indicated (18F)-fluorodeoxyglucose (FDG) PET/CT due to suspected or known lung cancer. The patients had a median age of 66 years (interquartile range [IQR]: 61-72 years). Segmentations were made manually by visual inspection in a consensus reading by two nuclear medicine specialists and used as a reference. The research prototype PARS was used to automatically analyse all the PET/CT studies. The PET foci classified as suspicious by PARS were compared with the manual segmentations. No manual corrections were applied. Total lesion glycolysis (TLG) was calculated based on the manual and PARS-based lung-tumour segmentations. Associations between TLG and OS were investigated using Cox analysis. RESULTS: PARS showed sensitivities for lung tumours of 55.6% per lesion and 80.2% per patient. Both manual and PARS TLG were significantly associated with OS. CONCLUSION: Automatically calculated TLG by PARS contains prognostic information comparable to manually measured TLG in patients with known or suspected lung cancer. The low sensitivity at both the lesion and patient levels makes the present version of PARS less useful to support clinical reading, reporting and staging.

Freely available convolutional neural network-based quantification of PET/CT lesions is associated with survival in patients with lung cancer.

BACKGROUND: Metabolic positron emission tomography/computed tomography (PET/CT) parameters describing tumour activity contain valuable prognostic information, but to perform the measurements manually leads to both intra- and inter-reader variability and is too time-consuming in clinical practice. The use of modern artificial intelligence-based methods offers new possibilities for automated and objective image analysis of PET/CT data. PURPOSE: We aimed to train a convolutional neural network (CNN) to segment and quantify tumour burden in [18F]-fluorodeoxyglucose (FDG) PET/CT images and to evaluate the association between CNN-based measurements and overall survival (OS) in patients with lung cancer. A secondary aim was to make the method available to other researchers. METHODS: A total of 320 consecutive patients referred for FDG PET/CT due to suspected lung cancer were retrospectively selected for this study. Two nuclear medicine specialists manually segmented abnormal FDG uptake in all of the PET/CT studies. One-third of the patients were assigned to a test group. Survival data were collected for this group. The CNN was trained to segment lung tumours and thoracic lymph nodes. Total lesion glycolysis (TLG) was calculated from the CNN-based and manual segmentations. Associations between TLG and OS were investigated using a univariate Cox proportional hazards regression model. RESULTS: The test group comprised 106 patients (median age, 76 years (IQR 61-79); n = 59 female). Both CNN-based TLG (hazard ratio 1.64, 95% confidence interval 1.21-2.21; p = 0.001) and manual TLG (hazard ratio 1.54, 95% confidence interval 1.14-2.07; p = 0.004) estimations were significantly associated with OS. CONCLUSION: Fully automated CNN-based TLG measurements of PET/CT data showed were significantly associated with OS in patients with lung cancer. This type of measurement may be of value for the management of future patients with lung cancer. The CNN is publicly available for research purposes.

Automated artificial intelligence-based analysis of skeletal muscle volume predicts overall survival after cystectomy for urinary bladder cancer.

BACKGROUND: Radical cystectomy for urinary bladder cancer is a procedure associated with a high risk of complications, and poor overall survival (OS) due to both patient and tumour factors. Sarcopenia is one such patient factor. We have developed a fully automated artificial intelligence (AI)-based image analysis tool for segmenting skeletal muscle of the torso and calculating the muscle volume. METHODS: All patients who have undergone radical cystectomy for urinary bladder cancer 2011-2019 at Sahlgrenska University Hospital, and who had a pre-operative computed tomography of the abdomen within 90 days of surgery were included in the study. All patients CT studies were analysed with the automated AI-based image analysis tool. Clinical data for the patients were retrieved from the Swedish National Register for Urinary Bladder Cancer. Muscle volumes dichotomised by the median for each sex were analysed with Cox regression for OS and logistic regression for 90-day high-grade complications. The study was approved by the Swedish Ethical Review Authority (2020-03985). RESULTS: Out of 445 patients who underwent surgery, 299 (67%) had CT studies available for analysis. The automated AI-based tool failed to segment the muscle volume in seven (2%) patients. Cox regression analysis showed an independent significant association with OS (HR 1.62; 95% CI 1.07-2.44; p = 0.022). Logistic regression did not show any association with high-grade complications. CONCLUSION: The fully automated AI-based CT image analysis provides a low-cost and meaningful clinical measure that is an independent biomarker for OS following radical cystectomy.

Artificial intelligence-based measurements of PET/CT imaging biomarkers are associated with disease-specific survival of high-risk prostate cancer patients.

OBJECTIVE: Artificial intelligence (AI) offers new opportunities for objective quantitative measurements of imaging biomarkers from positron-emission tomography/computed tomography (PET/CT). Clinical image reporting relies predominantly on observer-dependent visual assessment and easily accessible measures like SUVmax, representing lesion uptake in a relatively small amount of tissue. Our hypothesis is that measurements of total volume and lesion uptake of the entire tumour would better reflect the disease`s activity with prognostic significance, compared with conventional measurements. METHODS: An AI-based algorithm was trained to automatically measure the prostate and its tumour content in PET/CT of 145 patients. The algorithm was then tested retrospectively on 285 high-risk patients, who were examined using 18F-choline PET/CT for primary staging between April 2008 and July 2015. Prostate tumour volume, tumour fraction of the prostate gland, lesion uptake of the entire tumour, and SUVmax were obtained automatically. Associations between these measurements, age, PSA, Gleason score and prostate cancer-specific survival were studied, using a Cox proportional-hazards regression model. RESULTS: Twenty-three patients died of prostate cancer during follow-up (median survival 3.8 years). Total tumour volume of the prostate (p = 0.008), tumour fraction of the gland (p = 0.005), total lesion uptake of the prostate (p = 0.02), and age (p = 0.01) were significantly associated with disease-specific survival, whereas SUVmax (p = 0.2), PSA (p = 0.2), and Gleason score (p = 0.8) were not. CONCLUSION: AI-based assessments of total tumour volume and lesion uptake were significantly associated with disease-specific survival in this patient cohort, whereas SUVmax and Gleason scores were not. The AI-based approach appears well-suited for clinically relevant patient stratification and monitoring of individual therapy.

AI-based detection of lung lesions in [18F]FDG PET-CT from lung cancer patients.

BACKGROUND: [18F]-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET-CT) is a well-established modality in the work-up of patients with suspected or confirmed diagnosis of lung cancer. Recent research efforts have focused on extracting theragnostic and textural information from manually indicated lung lesions. Both semi-automatic and fully automatic use of artificial intelligence (AI) to localise and classify FDG-avid foci has been demonstrated. To fully harness AI's usefulness, we have developed a method which both automatically detects abnormal lung lesions and calculates the total lesion glycolysis (TLG) on FDG PET-CT. METHODS: One hundred twelve patients (59 females and 53 males) who underwent FDG PET-CT due to suspected or for the management of known lung cancer were studied retrospectively. These patients were divided into a training group (59%; n = 66), a validation group (20.5%; n = 23) and a test group (20.5%; n = 23). A nuclear medicine physician manually segmented abnormal lung lesions with increased FDG-uptake in all PET-CT studies. The AI-based method was trained to segment the lesions based on the manual segmentations. TLG was then calculated from manual and AI-based measurements, respectively and analysed with Bland-Altman plots. RESULTS: The AI-tool's performance in detecting lesions had a sensitivity of 90%. One small lesion was missed in two patients, respectively, where both had a larger lesion which was correctly detected. The positive and negative predictive values were 88% and 100%, respectively. The correlation between manual and AI TLG measurements was strong (R2 = 0.74). Bias was 42 g and 95% limits of agreement ranged from - 736 to 819 g. Agreement was particularly high in smaller lesions. CONCLUSIONS: The AI-based method is suitable for the detection of lung lesions and automatic calculation of TLG in small- to medium-sized tumours. In a clinical setting, it will have an added value due to its capability to sort out negative examinations resulting in prioritised and focused care on patients with potentially malignant lesions.

Artificial intelligence-aided CT segmentation for body composition analysis: a validation study.

BACKGROUND: Body composition is associated with survival outcome in oncological patients, but it is not routinely calculated. Manual segmentation of subcutaneous adipose tissue (SAT) and muscle is time-consuming and therefore limited to a single CT slice. Our goal was to develop an artificial-intelligence (AI)-based method for automated quantification of three-dimensional SAT and muscle volumes from CT images. METHODS: Ethical approvals from Gothenburg and Lund Universities were obtained. Convolutional neural networks were trained to segment SAT and muscle using manual segmentations on CT images from a training group of 50 patients. The method was applied to a separate test group of 74 cancer patients, who had two CT studies each with a median interval between the studies of 3 days. Manual segmentations in a single CT slice were used for comparison. The accuracy was measured as overlap between the automated and manual segmentations. RESULTS: The accuracy of the AI method was 0.96 for SAT and 0.94 for muscle. The average differences in volumes were significantly lower than the corresponding differences in areas in a single CT slice: 1.8% versus 5.0% (p < 0.001) for SAT and 1.9% versus 3.9% (p < 0.001) for muscle. The 95% confidence intervals for predicted volumes in an individual subject from the corresponding single CT slice areas were in the order of ± 20%. CONCLUSIONS: The AI-based tool for quantification of SAT and muscle volumes showed high accuracy and reproducibility and provided a body composition analysis that is more relevant than manual analysis of a single CT slice.

Artificial intelligence-based detection of lymph node metastases by PET/CT predicts prostate cancer-specific survival.

INTRODUCTION: Lymph node metastases are a key prognostic factor in prostate cancer (PCa), but detecting lymph node lesions from PET/CT images is a subjective process resulting in inter-reader variability. Artificial intelligence (AI)-based methods can provide an objective image analysis. We aimed at developing and validating an AI-based tool for detection of lymph node lesions. METHODS: A group of 399 patients with biopsy-proven PCa who had undergone 18 F-choline PET/CT for staging prior to treatment were used to train (n = 319) and test (n = 80) the AI-based tool. The tool consisted of convolutional neural networks using complete PET/CT scans as inputs. In the test set, the AI-based lymph node detections were compared to those of two independent readers. The association with PCa-specific survival was investigated. RESULTS: The AI-based tool detected more lymph node lesions than Reader B (98 vs. 87/117; p = .045) using Reader A as reference. AI-based tool and Reader A showed similar performance (90 vs. 87/111; p = .63) using Reader B as reference. The number of lymph node lesions detected by the AI-based tool, PSA, and curative treatment was significantly associated with PCa-specific survival. CONCLUSION: This study shows the feasibility of using an AI-based tool for automated and objective interpretation of PET/CT images that can provide assessments of lymph node lesions comparable with that of experienced readers and prognostic information in PCa patients.

RECOMIA-a cloud-based platform for artificial intelligence research in nuclear medicine and radiology.

BACKGROUND: Artificial intelligence (AI) is about to transform medical imaging. The Research Consortium for Medical Image Analysis (RECOMIA), a not-for-profit organisation, has developed an online platform to facilitate collaboration between medical researchers and AI researchers. The aim is to minimise the time and effort researchers need to spend on technical aspects, such as transfer, display, and annotation of images, as well as legal aspects, such as de-identification. The purpose of this article is to present the RECOMIA platform and its AI-based tools for organ segmentation in computed tomography (CT), which can be used for extraction of standardised uptake values from the corresponding positron emission tomography (PET) image. RESULTS: The RECOMIA platform includes modules for (1) local de-identification of medical images, (2) secure transfer of images to the cloud-based platform, (3) display functions available using a standard web browser, (4) tools for manual annotation of organs or pathology in the images, (5) deep learning-based tools for organ segmentation or other customised analyses, (6) tools for quantification of segmented volumes, and (7) an export function for the quantitative results. The AI-based tool for organ segmentation in CT currently handles 100 organs (77 bones and 23 soft tissue organs). The segmentation is based on two convolutional neural networks (CNNs): one network to handle organs with multiple similar instances, such as vertebrae and ribs, and one network for all other organs. The CNNs have been trained using CT studies from 339 patients. Experienced radiologists annotated organs in the CT studies. The performance of the segmentation tool, measured as mean Dice index on a manually annotated test set, with 10 representative organs, was 0.93 for all foreground voxels, and the mean Dice index over the organs were 0.86 (0.82 for the soft tissue organs and 0.90 for the bones). CONCLUSION: The paper presents a platform that provides deep learning-based tools that can perform basic organ segmentations in CT, which can then be used to automatically obtain the different measurement in the corresponding PET image. The RECOMIA platform is available on request at www.recomia.org for research purposes.

Deep learning-based quantification of PET/CT prostate gland uptake: association with overall survival.

AIM: To validate a deep-learning (DL) algorithm for automated quantification of prostate cancer on positron emission tomography/computed tomography (PET/CT) and explore the potential of PET/CT measurements as prognostic biomarkers. MATERIAL AND METHODS: Training of the DL-algorithm regarding prostate volume was performed on manually segmented CT images in 100 patients. Validation of the DL-algorithm was carried out in 45 patients with biopsy-proven hormone-naïve prostate cancer. The automated measurements of prostate volume were compared with manual measurements made independently by two observers. PET/CT measurements of tumour burden based on volume and SUV of abnormal voxels were calculated automatically. Voxels in the co-registered 18 F-choline PET images above a standardized uptake value (SUV) of 2·65, and corresponding to the prostate as defined by the automated segmentation in the CT images, were defined as abnormal. Validation of abnormal voxels was performed by manual segmentation of radiotracer uptake. Agreement between algorithm and observers regarding prostate volume was analysed by Sørensen-Dice index (SDI). Associations between automatically based PET/CT biomarkers and age, prostate-specific antigen (PSA), Gleason score as well as overall survival were evaluated by a univariate Cox regression model. RESULTS: The SDI between the automated and the manual volume segmentations was 0·78 and 0·79, respectively. Automated PET/CT measures reflecting total lesion uptake and the relation between volume of abnormal voxels and total prostate volume were significantly associated with overall survival (P = 0·02), whereas age, PSA, and Gleason score were not. CONCLUSION: Automated PET/CT biomarkers showed good agreement to manual measurements and were significantly associated with overall survival.

Artificial intelligence-based versus manual assessment of prostate cancer in the prostate gland: a method comparison study.

AIM: To test the feasibility of a fully automated artificial intelligence-based method providing PET measures of prostate cancer (PCa). METHODS: A convolutional neural network (CNN) was trained for automated measurements in 18 F-choline (FCH) PET/CT scans obtained prior to radical prostatectomy (RP) in 45 patients with newly diagnosed PCa. Automated values were obtained for prostate volume, maximal standardized uptake value (SUVmax ), mean standardized uptake value of voxels considered abnormal (SUVmean ) and volume of abnormal voxels (Volabn ). The product SUVmean  × Volabn was calculated to reflect total lesion uptake (TLU). Corresponding manual measurements were performed. CNN-estimated data were compared with the weighted surgically removed tissue specimens and manually derived data and related to clinical parameters assuming that 1 g ≈ 1 ml of tissue. RESULTS: The mean (range) weight of the prostate specimens was 44 g (20-109), while CNN-estimated volume was 62 ml (31-108) with a mean difference of 13·5 g or ml (95% CI: 9·78-17·32). The two measures were significantly correlated (r = 0·77, P<0·001). Mean differences (95% CI) between CNN-based and manually derived PET measures of SUVmax, SUVmean, Volabn (ml) and TLU were 0·37 (-0·01 to 0·75), -0·08 (-0·30 to 0·14), 1·40 (-2·26 to 5·06) and 9·61 (-3·95 to 23·17), respectively. PET findings Volabn and TLU correlated with PSA (P<0·05), but not with Gleason score or stage. CONCLUSION: Automated CNN segmentation provided in seconds volume and simple PET measures similar to manually derived ones. Further studies on automated CNN segmentation with newer tracers such as radiolabelled prostate-specific membrane antigen are warranted.

Contribution of SPECT/CT for sentinel node localization in patients with ipsilateral breast cancer relapse.

BACKGROUND: In recent years repeat sentinel node (SN) biopsy has been proven to be feasible in local breast cancer recurrence (LBCR). However, in these patients SNs outside the ipsilateral axilla are frequently observed. This study evaluates the contribution of SPECT/CT for SN localization and surgical adjustment in LBCR patients. METHODS: SN biopsy was performed in 122 LBCR patients (median age 60.5 years, range 24-87), enrolled from August 2006 to July 2015. Median disease-free time lapse was 109.5 months (range 9-365). Axillary lymph node dissection (ALND) had previously been performed in 55 patients, SN biopsy in 44, both techniques in 13 and fine-needle aspiration in 10. Primary breast cancer treatment included radiotherapy in 104 patients (85.3 %) and chemotherapy in 40 (32.8 %). Preoperative lymphatic mapping, using planar scintigraphy (PS) and SPECT/CT included report of SN location according to lymph node territory. In case of a territorial PS-SPECT/CT mismatch, surgery was adjusted according to SPECT/CT findings. RESULTS: SPECT/CT SN visualization rate was higher than PS (53.3 % vs. 43.4 %, p n.s.) with, in total, 19 additional SN (118 vs. 99, p n.s.). PS-SPECT/CT territory mismatch, found in 60 % (39/65) of patients with SN visualization, led to surgical adjustment in 21.3 % (26/122) of patients. The SN procedure was finally performed in 104 patients resulting in a 65.7 % surgical retrieval rate with a total of 132 removed SNs (1.86/patient). SN metastases were found in 17/71 patients (23.9 %), in 16 of them (94 %) in ipsilateral basins outside the axilla or in the contralateral axilla. CONCLUSION: Using SPECT/CT there is a trend to visualize more SNs in LBCR, providing at the same time important anatomical information to adjust intraoperative SN procedures. The addition of SPECT/CT to the standard imaging protocol may lead to better staging mainly in patients presenting drainage outside the ipsilateral axilla.