Volumetric Imaging System Research Articles

Integral imaging systems using interleaved Fresnel lenses and transmissive display panels

Integral imaging reproduces the light-ray space of a scene to realize a 3D vision. In particular, a coarse integral imaging system, featuring elemental lenses large enough to cover more pixels than the number of views, holds promise in applications like interactive visualization systems and automobile head-up displays (HUDs) for 3D display. However, conventional coarse integral imaging and coarse integral volumetric imaging systems face challenges related to visible seams in the lens array and the emergence of moiré patterns caused by layered liquid crystal panels (LCDs), that significantly degrade image quality. This paper presents a solution to these problems by employing an integrated interleaved Fresnel lens sheet to achieve seamless 3D images with smooth motion parallax while using layered transmissive panels to generate volumetric images free from moiré.

Coarse Integral Volumetric Imaging Display with Time and Polarization Multiplexing

This paper introduces an innovative approach to integral volumetric imaging employing time and polarization multiplexing techniques to present volumetric three-dimensional images. Traditional integral volumetric imaging systems with a coarse lens array often face moiré pattern issues stemming from layered panel structures. In response, our proposed system utilizes a combination of time and polarization multiplexing to achieve two focal planes using a single display panel.

Volumetric B-mode ultrasound and Doppler Imaging: Automatic Tracking With One Single Camera.

Vascular diseases may occur in the upper extremities, and the lesions can span the entire length of the blood vessel. One of the most popular methods to identify vascular disorders is ultrasound Doppler imaging. However, traditional two-dimensional (2D) ultrasound Doppler imaging cannot capture the entire length of a long vessel in one image. Medical professionals often have to painstakingly reconstruct three-dimensional (3D) data using 2D ultrasound images to locate the lesions, especially for large blood vessels. 3D ultrasound Doppler imaging can display the morphological structure of blood vessels and the distribution of lesions more directly, providing a more comprehensive view compared to 2D imaging. In this work, we propose a wide-range 3D volumetric ultrasound Doppler imaging system with dual modality, in which a high-definition camera is adopted to automatically track the movement of the ultrasound transducer, simultaneously capturing a corresponding sequence of 2D ultrasound Doppler images. We conducted experiments on human arms using our proposed system and separately with X-ray computerized tomography (X-CT). The comparison results prove the potential value of our proposed system in the diagnosis of arm vascular diseases.

3D volumetric imaging system based on a carbon-based light-induced ultrasound transmitter

3D volumetric imaging system based on a carbon-based light-induced ultrasound transmitter

Panoramic volumetric clinical handheld photoacoustic and ultrasound imaging

Photoacoustic (PA) imaging has gained much attention, providing structural and functional information in combination with clinical ultrasound (US) imaging systems. 2D PA and US imaging is easily implemented, but its heavy dependence on operator skills makes 3D imaging preferable. In this study, we propose a panoramic volumetric clinical PA and US imaging system equipping a handheld imaging scanner weighing 600 g and measuring 70 × 62 × 110 mm3. Multiple PA/US scans were performed to cover a large field-of-view (FOV), and the acquired PA/US volumes were mosaic-stitched after manually correcting the positions and rotations in a total of 6 degrees of freedom. PA and US maximum amplitude projection images were visualized online, while spectral unmixed data was quantified offline. The performance of the system was tested via tissue-mimicking phantom experiments. The system’s potential was confirmed in vivo by panoramically imaging vascular networks in human arms and necks, with FOVs of 331 × 38 and 129 × 120 mm2, respectively. Further, we quantified hemoglobin oxygen saturation levels in the radial artery, brachial artery, carotid artery, and jugular vein. We hope that this system can be applied for various clinical fields such as cardiovascular imaging, dermatology, vascular surgery, internal medicine, and oncology.

Rapid Cellular-Resolution Skin Imaging with Optical Coherence Tomography Using All-Glass Multifocal Metasurfaces.

Cellular-resolution optical coherence tomography (OCT) is a powerful tool offering noninvasive histology-like imaging. However, like other optical microscopy tools, a high numerical aperture (N.A.) lens is required to generate a tight focus, generating a narrow depth of field, which necessitates dynamic focusing and limiting the imaging speed. To overcome this limitation, we developed a metasurface platform that generates multiple axial foci, which multiplies the volumetric OCT imaging speed by offering several focal planes. This platform offers accurate and flexible control over the number, positions, and intensities of axial foci generated. All-glass metasurface optical elements 8 mm in diameter are fabricated from fused-silica wafers and implemented into our scanning OCT system. With a constant lateral resolution of 1.1 μm over all depths, the multifocal OCT triples the volumetric acquisition speed for dermatological imaging, while still clearly revealing features of stratum corneum, epidermal cells, and dermal-epidermal junctions and offering morphological information as diagnostic criteria for basal cell carcinoma. The imaging speed can be further improved in a sparse sample, e.g., 7-fold with a seven-foci beam. In summary, this work demonstrates the concept of metasurface-based multifocal OCT for rapid virtual biopsy, further providing insights for developing rapid volumetric imaging systems with high resolution and compact volume.

Real-time, volumetric imaging of radiation dose delivery deep into the liver during cancer treatment.

Ionizing radiation acoustic imaging (iRAI) allows online monitoring of radiation's interactions with tissues during radiation therapy, providing real-time, adaptive feedback for cancer treatments. We describe an iRAI volumetric imaging system that enables mapping of the three-dimensional (3D) radiation dose distribution in a complex clinical radiotherapy treatment. The method relies on a two-dimensional matrix array transducer and a matching multi-channel preamplifier board. The feasibility of imaging temporal 3D dose accumulation was first validated in a tissue-mimicking phantom. Next, semiquantitative iRAI relative dose measurements were verified in vivo in a rabbit model. Finally, real-time visualization of the 3D radiation dose delivered to a patient with liver metastases was accomplished with a clinical linear accelerator. These studies demonstrate the potential of iRAI to monitor and quantify the 3D radiation dose deposition during treatment, potentially improving radiotherapy treatment efficacy using real-time adaptive treatment.

Investigation of Computed Tomography Numbers on Multiple Imaging Systems using Single and Multislice Methods.

The aim of this study is to determine the variation in Hounsfield values with single and multi-slice methods using in-house software on fan-beam computed tomography (FCT), linear accelerator (linac) cone-beam computed tomography (CBCT), and Icon-CBCT datasets acquired using Gammex and advanced electron density (AED) phantoms. The AED phantom was scanned on a Toshiba computed tomography (CT) scanner, five linac-based CBCT X-ray volumetric imaging systems, and Leksell Gamma Knife Icon. The variation between single and multi-slice methods was assessed by comparing scans acquired using Gammex and AED phantoms. The variation in Hounsfield units (HUs) between seven different clinical protocols was assessed using the AED phantom. A CIRS Model 605 Radiosurgery Head Phantom (TED) phantom was scanned on all three imaging systems to assess the target dosimetric changes due to HU variation. An in-house software was developed in MATLAB to assess the HU statistics and the trend along the longitudinal axis. The FCT dataset showed a minimal variation (central slice ± 3 HU) in HU values along the long axis. A similar trend was also observed between the studied clinical protocols acquired on FCT. Variation among multiple linac CBCTs was insignificant. In the case of the water insert, a maximum HU variation of -7.23 ± 68.67 was observed for Linac 1 towards the inferior end of the phantom. All five linacs appeared to have a similar trend in terms of HU variation from the proximal to the distal end of the phantom, with a few outliers for Linac 5. Among three imaging modalities, the maximum variation was observed in gamma knife CBCTs, whereas FCT showed no appreciable deviation from the central value. In terms of dosimetric comparison, the mean dose in CT and Linac CBCT scans differed by <0.5 Gy, whereas at least a 1 Gy difference was observed between CT and gamma knife CBCT. This study shows a minimal variation with FCT between single, volume-based, and multislice methods, and hence the current approach of determining the CT-electron density curve based on a single-slice method would be sufficient for producing a HU calibrations curve for treatment planning. However, CBCTs acquired on linac, and in particular, gamma knife systems, show noticeable variations along the long axis, which is likely to affect the dose calculations performed on CBCTs. It is highly recommended to assess the Hounsfield values on multiple slices before using the HU curve for dose calculations.

THE INFORMATIVE VALUE OF MAGNETIC RESONANCE IMAGING IN THE DIAGNOSIS OF RECTAL TUMOR INVOLVEMENT AGAINST THE BACKGROUND OF COMBINED TREATMENT

The aim of the study is to prove the informative value of magnetic resonance imaging in the diagnosis of rectal tumor involvement against the background of combined treatment for the patients (chemotherapy + radiation therapy) on the basis of the AI "Republican Oncological Dispensary", Cheboksary. All patients underwent magnetic resonance imaging on Elekta Synergy linear accelerator with a multi-leaf collimator, an integrated XVI X-ray volumetric imaging system and iViewGT portal imaging system, Mosaiq information and control system. Statistical processing was performed using standard methods of medical statistics using the SPSS Statistics package (version 17.0), arithmetic mean (M), standard deviation from the general mean age, mean value errors (m), Student's t-test were also calculated. Magnetic resonance imaging diagnostics made it possible to identify and dynamically control the change in the tumor involvement of the rectum against the background of the treatment: a change in the localization of the tumor in different parts of the rectum, a change in localization depending on the distance from the anal margin, a change in the thickness of the tumor wall, a change in the size and number of lymph nodes. Extramural venous invasion (EMVI), marginal resection boundary (CRM) of the tumor and invasion into surrounding tissues after surgical intervention were evaluated. This article examines the incidence of rectal cancer depending on age, gender, complaints, oncological history, risk factors contributing to the development of this pathology, as well as the presence of concomitant diseases that aggravate treatment. According to the results of the study, rectal cancer is revealed to be most often found in people aged 60–70, while men are most susceptible to the disease. According to histomorphological data, adenocarcinoma prevailed in 94 persons. Rectal cancer before and after chemoradiotherapy, according to magnetic resonance imaging (MRI) findings, prevailed in the rectal lower ampulla (before chemoradiotherapy – in 51 persons, after chemoradiotherapy – in 48), while the malignant neoplasm was at the distance of 21-30 mm from the anal margin in 27 persons, with the average wall thickness of 21.5 mm according to MRI findings before chemoradiotherapy and 13.9 mm after chemoradiotherapy. The difference in the average wall thickness according to the findings of two MRI studies was 7.61 mm (33.3%), which indicates the effectiveness of chemoradiotherapy.

A multi-modal volumetric microscope with automated sample handling for surveying microbial life in liquid samples

In the study of microbial life, microscopy plays a unique role due to its ability to detect ordered structure, motility, and fluorescence signals. As such it has also recently gained attention in the context of searching for extant life on distant Solar System bodies bearing liquid water. In this paper we introduce a multi-modal volumetric microscopy system for potential future spaceflight missions that combines digital holographic microscopy (DHM) and volume fluorescence imager (VFI), which are volumetric imaging methods that provide high-resolution, high-throughput examination of liquid samples. DHM provides information on the absorption, morphology, and motility of imaged objects without requiring the use of contrast agents. On the other hand, VFI based on light field microscopy focuses on the fluorescence signals from the sample to observe specific structures dyed with targeted contrast agents or providing unique autofluorescence signals. We also present an autonomous sample handling and data acquisition system to allow for an autonomous mission to distant planets or moons, or for autonomous use in bodies of water on Earth. The full system, named ELVIS, or Extant Life Volumetric Imaging System, is capable of autonomously surveying a liquid sample to extract morphology, motility, and fluorescence signals of extant microbial life.

Scalable tissue labeling and clearing of intact human organs

Advances in tissue labeling and clearing methods include improvement of tissue transparency, better preservation of fluorescence signal, compatibility with immunostaining and large sample volumes. However, as existing methods share the common limitation that they can only be applied to human tissue slices, rendering intact human organs transparent remains a challenge. Here, we describe experimental details of the small-micelle-mediated human organ efficient clearing and labeling (SHANEL) pipeline, which can be applied for cellular mapping of intact human organs. We have successfully cleared multiple human organs, including kidney, pancreas, heart, lung, spleen and brain, as well as hard tissue like skull. We also describe an advanced volumetric imaging system using a commercial light-sheet fluorescence microscope that can accommodate most human organs and a pipeline for whole-organ imaging and visualization. The complete experimental process of labeling and clearing whole human organs takes months and the analysis process takes several weeks, depending on the organ types and sizes.

Evaluation of optimal kilovoltage-cone beam technique on image quality, registration accuracy, time of imaging and relative dose for head radiotherapy: A phantom study

Background: Image-guided radiation therapy (IGRT) has improved geometry accuracy of patient positioning in radiotherapy. Nowadays, a kilo-voltage cone-beam computed tomography (kV-CBCT) is widely applied in IGRT to confirm daily patient positioning. However, one problem with IGRT is the increased dose to normal tissue outside the target area. Reduction in the dose of kV-CBCT verification imaging leads to deterioration in image quality and registration results. Objectives: The objective of this study was to evaluate an optimal kV cone-beam technique on image quality, registration accuracy, relative dose, and imaging time using different combinations of angular range, angular separation, and mA (in total eight protocols) in the head phantom. Materials and methods: Catphan® 503 phantom was used to evaluate image quality and a PIXY Anthropomorphic Training/Teaching Phantom was used to verify image registration accuracy. The kV-CBCT imaging was performed using an X-ray volumetric imaging (XVI) system mounted on an Elekta Versa HD linear accelerator. The absorbed dose of kV-CBCT imaging was determined using the head phantom with an ionization chamber. The eight protocols were analyzed for image quality, image registration, relative dose change, and imaging delivery time. Results: Image quality parameter results showed that maximum contrast to noise ratio (CNR) increased by approximately 65% at 100 kV, 20 mA, θ=360°, and Δθ=0.54°, while uniformity compared with 100 kV, 10 mA, θ=200°, Δθ=0.54° (default protocol) varied within 7%. The spatial resolution showed no change (0.167 cm), with geometric distortions of less than 0.2 mm. Image registration errors were within 0.2 cm, with the highest magnitude of error seen in the vertical direction. Imaging dose can be reduced using 100 kV, 10 mA, θ=200°, Δθ=1.09° about 50% and 100 kV, 10 mA, θ=360°, Δθ=1.09° about 15% with similar CNR of default protocol. Imaging time decreased by approximately 2-folds, while Δθ increased by 2-folds. Conclusion: The suggested protocols suitable for optimal kV-CBCT image quality, accuracy of image registration, decreased imaging time, and reduced image dose in the head region were 1) 10 mA, θ=200°, Δθ=1.09° 2) 10 mA, θ=360°, Δθ=1.09°, and 3) 20 mA, θ=360°, Δθ=1.09°. These protocols decreased imaging dose about 50%, 15%, and 2%, respectively. The developing kV-CBCT technique should be counterbalanced by careful consideration of imaging dose, image quality, imaging time, and accuracy of image registration.

3D Volumetric Imaging System Based on a Carbon-Based Light-Induced Ultrasound Transmitter

3D Volumetric Imaging System Based on a Carbon-Based Light-Induced Ultrasound Transmitter

WITHDRAWN: Cardiac chamber analysis by volumetric assessment IN cardiovascular imaging systems- A review

Cardiovascular diseases are the leading causes of death and it increasing the mortality rate over the decades. Historically, the diagnosis of any forms of cardiovascular diseases has depended on cardiac output measurements which are invasive techniques. In recent days, Echocardiography, Cardiac Computed Tomography (CCT), Cardiac Magnetic resonance (CMR), Nuclear imaging (CT-SPECT) is evolved to diagnose the cardiovascular diseases in non-invasive manner. As like cardiac output in invasive techniques, the stroke volume, ejection fraction and other volumetric parameters acts as a predictive markers to diagnose CVD and cardiac chamber analysis in non invasive techniques. The different methods like geometrical assumptions, contour tracing, automatic method used to evaluate the volumetric parameters are reviewed in this article. The importance of Ejection fraction in diagnosis of cardiovascular diseases and the analysis of cardiac function are outlined. This extensive review analyses the literature associated with modalities and the methods involved in diagnosis of cardiovascular diseases and also the analysis of cardiac function. Also summarizes the recent reports in the field of cardiovascular imaging along with their pros and cons.

A Novel Use of Hydrogel as a Dual-Buffer in Stereotactic Body Proton Therapy for Locally Advanced Pancreatic Cancer

To evaluate the dosimetric efficacy of using hydrogel as a dual buffer, namely to suppress the dose to duodenum and boost the plan robustness in stereotactic body proton therapy for locally advanced pancreatic cancer. The dosimetric advantages of hydrogel spacer is quantitatively evaluated by a proposed quantity, full-width-half-maximum (FWHM) of dose spread function (DSF), which is defined as the distance needed to dwindle dose 50% off to the duodenum. The dose spread function is the derivative of dose falloff profile along the neighboring of 100% isodose line and critical organ. A proof-of-concept study was implemented on one of the previously treated pancreatic patients with prescribed dose of 33 Gy (RBE) in 5 fractions using spot scanning proton beam. The gross target volume is expanded with 2 mm using on-board volumetric imaging system to an optimization target volume (OTV). The proton plan dose profile in the abutment region between 100% isodose line and duodenum is sampled. The dose falloff is differentiated to obtain the FWHM distance to lower the dose to a 50% level. For all voxels representing the surface of duodenum, the mean values of FWHMs is therefore determined as the required spacing from hydrogel injection. An organ deformation method is developed to simulate the hydrogel spacer included in the post-injection plan, which is compared dosimetrically with pre-injection plan. The plan robust evaluation of the target coverage was assessed with 2 mm setup and 3.5% range uncertainties, defined as the percentage of the disturbed scenarios meeting the goal of more than 95% of target covered by at least 100% of the prescribed dose. The target coverages of both pre-injection and post-injection plans are able to achieve D98% with about 99% of the prescription. The required hydrogel spacing FWHM (mean distance for duodenum dose dropping to 50%) is determined as 14.1 mm. The average dose for duodenum in the hydrogel pre-injection plan is 7.35 Gy (RBE), while for post-injection plan is 4.61 Gy (RBE). By simulating the organ deformation induced by hydrogel spacing using the pre-determined value of FWHM, the dose covering 50% volume of the duodenum is lowered from 3.67 Gy (RBE) of pre-injection plan to 1.77 Gy (RBE) in the simulated post-injection plan, which is consistent with estimation using FWHM value. The high dose region to duodenum is also lowered for D2cc from 28 Gy (RBE) to 20.9 Gy (RBE). The robustness evaluation indicates that the passing rate of pre-injection plan is only 7%, while for the simulated post-injection plan is 21%. This study indicates that a hydrogel in SBPT can function dual roles as decreasing the dose to duodenum and improving the robustness of the post-injection pancreatic plan. With the knowledge of FWHM from DSF, the required spacing from hydrogel is determined. The dose level in post-injection plan match the desired dose level. The post-injection plan also demonstrates the improved immunity to range uncertainties and setup errors.

Single-Shot Near-Field Volumetric Imaging System for Optical Ultrasound and Photoacoustics Using Capacitive Micromachined Ultrasonic Transducer Without Transmission Mode.

In this article, we present a single-shot dual-mode imaging system that uses optical ultrasound (US) as an ultrasonic pulser without a transmission circuit. The ultrasonic pulse-echo system comprises an optical US pulser generated by carbon nanotubes (CNTs), which generate a high-power photoacoustic (PA) signal and a capacitive micromachined ultrasonic transducer (CMUT) receiver. By fabricating a thin CNT-polydimethylsiloxane (PDMS) composite capable of semiabsorption of the laser, a single-shot imaging system was developed. By transmitting a semipenetration light to the object, US and PA imaging were performed in a single shot. A CNT thickness of [Formula: see text] produced a maximum pressure of 154 kPa, and US was received by CMUT with a 2-MHz center frequency in PDMS. Additionally, a low-profile and near-depth imaging system was constructed with an intermediate layer of the 6-mm PDMS for the dry contact method. We performed a single-shot dual-mode imaging experiment on point and line phantoms, as well as the particle spread in the soft tissue. Thus, we examined the feasibility of the near-depth and single-shot dual-mode (US and PA) imaging system capable of a dry contact.

Commissioning experience of the X-ray volume imaging system of an image-guided radiotherapy capable linear accelerator

AbstractAim:An image-guided radiotherapy capable linear accelerator was installed at our hospital which is equipped with an X-ray volumetric imaging (XVI) system. The aim of this study was to describe the results of acceptance tests which were carried out on the XVI facility to verify the manufacturer’s specification.Materials and methods:The commissioning test had six elements: system safety, geometric accuracy, image quality, registration and correction accuracy, X-ray tube and generator performance, and quality assurance (QA) procedures.Results:We had satisfactory results for all the tests. The system passed the safety testes, and the agreement of isocentres was found to be within the tolerance limit. Imaging quality was acceptable. Registration and correction accuracy was tasted with indigenously developed phantom and positioned accurately at isocentre. X-ray tube and generator test results showed that the tube was performing properly.Findings:The described tests represent that the performance of the system is maintained at acceptable levels.

Development of a Handheld Volumetric Photoacoustic Imaging System With a Central-Holed 2D Matrix Aperture.

Photoacoustics has been evolving rapidly in the recent several decades. With the aim of clinical translation, a photoacoustic imaging platform with a portable system size, a miniaturized imaging probe, and convenient handheld capability is of great demand. In this work, by adopting an ultrathin central-holed matrix array and a compact coaxial photoacoustic design, a water-free handheld photoacoustic imager is developed (weight: 44 g). Optical Monte Carlo simulation and acoustic k-wave simulation are performed to confirm a relatively homogenous photoacoustic sensitivity distribution within a wide field of view (larger than 10 × 10 × 10mm3). Imaging resolution characterized by imaging two hairs is estimated to be about 0.80mm in the lateral direction and 0.73mm in the axial direction. To demonstrate the handheld capability in real time, handheld imaging guided needle biopsy in the rat's abdomen is performed at a rate of about 10 Hz (CNR ∼ 14.3dB). Furthermore, handheld imaging is also demonstrated on visualizing vasculature (mainly cephalic vein) in the human arm (CNR > 4.1dB). Results demonstrate that the volumetric photoacoustic imaging system using a central-holed 2D matrix array is an attractive choice for achieving convenient handheld operation in real time. Such a compact handheld design may promote the clinical translation of photoacoustic technique.

Image quality improvement for medium and large field of view Elekta XVI scans.

Cone-beam computed tomography (CBCT) has become the standard imaging technique for many sites treated with Radiotherapy. The Elekta X-ray Volumetric Imaging (XVI) system allows for the acquisition of CBCTs with three different diameters; small (27cm), medium (41cm) and large (50cm) (Elekta in XVI Corrective Maintenance Manual R5.0, Elekta, Stockholm, 2013). Images are used to ensure accurate patient positioning as well as checking for changes in the patient contour or internal geometry, and image quality must be high enough to achieve these goals. This paper describes two simple adjustments which can lead to improved image quality for medium and large field of view (MFOV and LFOV) scans. The first involves measuring a default distance in the XVI software (kV Source to Detector Distance) to improve spatial resolution and geometric scaling of both MFOV and LFOV scans. The second involves correcting a uniformity issue seen at our centre with LFOV scans, allowing us to use this FOV for assessing patient contour changes on large patients. The implementation and effects of both adjustments are explored in this paper, and workflows are proposed for optimising both parameters.

A Case-Control Study to Add Volumetric or Clinical Mammographic Density into the Tyrer-Cuzick Breast Cancer Risk Model.

BackgroundAccurate breast cancer risk assessment for women attending routine screening is needed to guide screening and preventive interventions. We evaluated the accuracy of risk predictions from both visual and volumetric mammographic density combined with the Tyrer-Cuzick breast cancer risk model.MethodsA case-control study (474 patient participants and 2243 healthy control participants) of women aged 40–79 years was performed using self-reported classical risk factors. Breast density was measured by using automated volumetric software and Breast Imaging and Reporting Data System (BI-RADS) density categories. Odds ratios (95% CI) were estimated by using logistic regression, adjusted for age, demographic factors, and 10-year risk from the Tyrer-Cuzick model, for a change from the 25th to 75th percentile of the adjusted percent density distribution in control participants (IQ-OR).ResultsAfter adjustment for classical risk factors in the Tyrer-Cuzick model, age, and body mass index (BMI), BI-RADS density had an IQ-OR of 1.55 (95% CI = 1.33 to 1.80) compared with 1.40 (95% CI = 1.21 to 1.60) for volumetric percent density. Fibroglandular volume (IQ-OR = 1.28, 95% CI = 1.12 to 1.47) was a weaker predictor than was BI-RADS density (Pdiff = 0.014) or volumetric percent density (Pdiff = 0.065). In this setting, 4.8% of women were at high risk (8% + 10-year risk), using the Tyrer-Cuzick model without density, and 7.1% (BI-RADS) compared with 6.8% (volumetric) when combined with density.ConclusionThe addition of volumetric and visual mammographic density measures to classical risk factors improves risk stratification. A combined risk could be used to guide precision medicine, through risk-adapted screening and prevention strategies.