Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

nuclear medicine; diagnostic radiolog

Virtual clinical trials in medical imaging: a review

The accelerating complexity and variety of medical imaging devices and methods have outpaced the ability to evaluate and optimize their design and clinical use. This is a significant and increasing challenge for both scientific investigations and clinical applications. Evaluations would ideally be done using clinical imaging trials. These experiments, however, are often not practical due to ethical limitations, expense, time requirements, or lack of ground truth. Virtual clinical trials (VCTs) (also known as in silico imaging trials or virtual imaging trials) offer an alternative means to efficiently evaluate medical imaging technologies virtually. They do so by simulating the patients, imaging systems, and interpreters. The field of VCTs has been constantly advanced over the past decades in multiple areas. We summarize the major developments and current status of the field of VCTs in medical imaging. We review the core components of a VCT: computational phantoms, simulators of different imaging modalities, and interpretation models. We also highlight some of the applications of VCTs across various imaging modalities

Non-Invasive Imaging for the Assessment of Cardiac Dose and Function Following Focused External Beam Irradiation

Technological advances in imaging and radiotherapy have led to significant improvement in the survival rate of breast cancer patients. However, a larger proportion of patients are now exhibiting the less understood, latent effects of incidental cardiac irradiation that occurs during left-sided breast radiotherapy. Here, we examine the utility of four-dimensional computed tomography (4D-CT) for the accurate assessment of cardiac dose; and a hybrid positron emission tomography (PET) magnetic resonance imaging (MRI) system to longitudinally study radiation-induced cardiac effects in a canine model. Using 4D-CT and deformable dose accumulation, we assessed the variation caused by breathing motion in the estimated dose to the heart, left-ventricle, and left anterior descending artery (LAD) of left-sided breast cancer patients. The LAD showed substantial variation in dose due to breathing. In light of this, we suggest the use of 4D-CT and dose accumulation for future clinical studies looking at the relationship between LAD dose and cardiac toxicity. Although symptoms of cardiac dysfunction may not manifest clinically for 10-15 years post radiation, PET-MRI can potentially identify earlier changes in cardiac inflammation and perfusion that are typically asymptomatic. Using PET-MRI, the progression of radiation-induced cardiac toxicity was assessed in a large animal model. Five canines were imaged using 13N-ammonia and 18F-fluorodeoxyglucose (FDG) PET-MRI to assess changes in myocardial perfusion and inflammation, respectively. All subjects were imaged at baseline, 1 week, 4 weeks, 3 months, 6 months, and 12 months after focused cardiac irradiation. To the best of our knowledge PET has not been previously used to assess cardiac perfusion following irradiation. The delivered dose to the heart, left ventricle, LAD, and left circumflex artery were comparable to what has been observed during breast radiotherapy. Relative to baseline, a transient increase in myocardial perfusion was observed followed by a gradual return to baseline. However, a persistent increase in FDG uptake was observed throughout the entire left ventricle, including both irradiated and less-irradiated portions of the heart. In light of these findings, we suggest the use of this imaging approach for future human studies to assess mitigation strategies aimed at minimizing cardiac exposure and long-term toxicity subsequent to left-sided breast irradiation

Applications of Rapid Cardiac Micro-CT

Mouse models are an important tool in cardiovascular disease research and a non-invasive imaging method is an advantageous way of monitoring disease progression. Cardiac micro-CT is rapid imaging technique capable of quantifying changes in cardiac structure and function in mice. The goal of this thesis was to demonstrate the utility of this technique in monitoring disease progression in a longitudinal study, as well as its capability for evaluating other methods of measuring cardiac function in mice. In a longitudinal study, a mouse model of myocardial infarction was scanned weekly for four weeks; left ventricular volume and ejection fraction were measured from the images. Cardiac micro-CT was capable of tracking small changes in cardiac structure and function, with the MI mice demonstrating a significant increase in volume and a significant decrease in ejection fraction. Both inter- and intra-variability was low, indicating the results were highly reproducible. Contrast agents are essential to evaluating the heart in micro-CT images. A new blood-pool agent was evaluated to determine its suitability for use in cardiac micro-CT studies. The agent produced excellent enhancement for the first 30 minutes post-injection, and had a unique characteristic of enhancing the myocardium, which may prove useful in studies evaluating wall motion. The effect of x-ray dose delivered during a longitudinal micro-CT study was also evaluated. C57BL/6 mice were scanned weekly for six weeks; the total entrance dose delivered over the study was 5.04 Gy. No significant changes to the heart or lungs were detectable on the micro-CT images at six weeks, and the histology performed on myocardial and pulmonary tissue showed no indication of early inflammation at a cellular level. Micro-CT can therefore be used in longitudinal studies without concern of adverse effects. Cardiac micro-CT was used to evaluate conductance catheters, and found that the catheter volumes were drastically underestimated compared to the micro-CT volumes. It was also determined that catheterization has the potential for causing cardiac enlargement; 40% of the mice demonstrated enlarged hearts following the catheterization procedure. Overall, cardiac-gated micro-CT is a rapid and reproducible imaging technique, and is proving to be valuable tool in cardiovascular disease research

Clinical quantitative cardiac imaging for the assessment of myocardial ischaemia

Cardiac imaging has a pivotal role in the prevention, diagnosis and treatment of ischaemic heart disease. SPECT is most commonly used for clinical myocardial perfusion imaging, whereas PET is the clinical reference standard for the quantification of myocardial perfusion. MRI does not involve exposure to ionizing radiation, similar to echocardiography, which can be performed at the bedside. CT perfusion imaging is not frequently used but CT offers coronary angiography data, and invasive catheter-based methods can measure coronary flow and pressure. Technical improvements to the quantification of pathophysiological parameters of myocardial ischaemia can be achieved. Clinical consensus recommendations on the appropriateness of each technique were derived following a European quantitative cardiac imaging meeting and using a real-time Delphi process. SPECT using new detectors allows the quantification of myocardial blood flow and is now also suited to patients with a high BMI. PET is well suited to patients with multivessel disease to confirm or exclude balanced ischaemia. MRI allows the evaluation of patients with complex disease who would benefit from imaging of function and fibrosis in addition to perfusion. Echocardiography remains the preferred technique for assessing ischaemia in bedside situations, whereas CT has the greatest value for combined quantification of stenosis and characterization of atherosclerosis in relation to myocardial ischaemia. In patients with a high probability of needing invasive treatment, invasive coronary flow and pressure measurement is well suited to guide treatment decisions. In this Consensus Statement, we summarize the strengths and weaknesses as well as the future technological potential of each imaging modality

LROC Investigation of Three Strategies for Reducing the Impact of Respiratory Motion on the Detection of Solitary Pulmonary Nodules in SPECT

The objective of this investigation was to determine the effectiveness of three motion reducing strategies in diminishing the degrading impact of respiratory motion on the detection of small solitary pulmonary nodules (SPNs) in single-photon emission computed tomographic (SPECT) imaging in comparison to a standard clinical acquisition and the ideal case of imaging in the absence of respiratory motion. To do this nonuniform rational B-spline cardiac-torso (NCAT) phantoms based on human-volunteer CT studies were generated spanning the respiratory cycle for a normal background distribution of Tc-99 m NeoTect. Similarly, spherical phantoms of 1.0-cm diameter were generated to model small SPN for each of the 150 uniquely located sites within the lungs whose respiratory motion was based on the motion of normal structures in the volunteer CT studies. The SIMIND Monte Carlo program was used to produce SPECT projection data from these. Normal and single-lesion containing SPECT projection sets with a clinically realistic Poisson noise level were created for the cases of 1) the end-expiration (EE) frame with all counts, 2) respiration-averaged motion with all counts, 3) one fourth of the 32 frames centered around EE (Quarter Binning), 4) one half of the 32 frames centered around EE (Half Binning), and 5) eight temporally binned frames spanning the respiratory cycle. Each of the sets of combined projection data were reconstructed with RBI-EM with system spatial-resolution compensation (RC). Based on the known motion for each of the 150 different lesions, the reconstructed volumes of respiratory bins were shifted so as to superimpose the locations of the SPN onto that in the first bin (Reconstruct and Shift). Five human observers performed localization receiver operating characteristics (LROC) studies of SPN detection. The observer results were analyzed for statistical significance differences in SPN detection accuracy among the three correction strategies, the standard acquisition, and the ideal case of the absence of respiratory motion. Our human-observer LROC determined that Quarter Binning and Half Binning strategies resulted in SPN detection accuracy statistically significantly below (P \u3c 0.05) that of standard clinical acquisition, whereas the Reconstruct and Shift strategy resulted in a detection accuracy not statistically significantly different from that of the ideal case. This investigation demonstrates that tumor detection based on acquisitions associated with less than all the counts which could potentially be employed may result in poorer detection despite limiting the motion of the lesion. The Reconstruct and Shift method results in tumor detection that is equivalent to ideal motion correction

Developments in PET-MRI for Radiotherapy Planning Applications

The hybridization of magnetic resonance imaging (MRI) and positron emission tomography (PET) provides the benefit of soft-tissue contrast and specific molecular information in a simultaneous acquisition. The applications of PET-MRI in radiotherapy are only starting to be realised. However, quantitative accuracy of PET relies on accurate attenuation correction (AC) of, not only the patient anatomy but also MRI hardware and current methods, which are prone to artefacts caused by dense materials. Quantitative accuracy of PET also relies on full characterization of patient motion during the scan. The simultaneity of PET-MRI makes it especially suited for motion correction. However, quality assurance (QA) procedures for such corrections are lacking. Therefore, a dynamic phantom that is PET and MR compatible is required. Additionally, respiratory motion characterization is needed for conformal radiotherapy of lung. 4D-CT can provide 3D motion characterization but suffers from poor soft-tissue contrast. In this thesis, I examine these problems, and present solutions in the form of improved MR-hardware AC techniques, a PET/MRI/CT-compatible tumour respiratory motion phantom for QA measurements, and a retrospective 4D-PET-MRI technique to characterise respiratory motion. Chapter 2 presents two techniques to improve upon current AC methods that use a standard helical CT scan for MRI hardware in PET-MRI. One technique uses a dual-energy computed tomography (DECT) scan to construct virtual monoenergetic image volumes and the other uses a tomotherapy linear accelerator to create CT images at megavoltage energies (1.0 MV) of the RF coil. The DECT-based technique reduced artefacts in the images translating to improved μ-maps. The MVCT-based technique provided further improvements in artefact reduction, resulting in artefact free μ-maps. This led to more AC of the breast coil. In chapter 3, I present a PET-MR-CT motion phantom for QA of motion-correction protocols. This phantom is used to evaluate a clinically available real-time dynamic MR images and a respiratory-triggered PET-MRI protocol. The results show the protocol to perform well under motion conditions. Additionally, the phantom provided a good model for performing QA of respiratory-triggered PET-MRI. Chapter 4 presents a 4D-PET/MRI technique, using MR sequences and PET acquisition methods currently available on hybrid PET/MRI systems. This technique is validated using the motion phantom presented in chapter 3 with three motion profiles. I conclude that our 4D-PET-MRI technique provides information to characterise tumour respiratory motion while using a clinically available pulse sequence and PET acquisition method