Positron emission tomography (PET) imaging has emerged as a standard component for cancer diagnosis treatment and has increasing use in clinical trials of new therapies for cancer and other diseases. The use of PET imaging to assess response to therapy and its ability to measure change in radiotracer uptake is motivated by its potential for quantitative accuracy and high sensitivity. However, the effectiveness depends upon a number of factors, including both the bias and variance in the pre- and post-therapy reconstructed images. Despite all the attention paid to image reconstruction algorithms, little attention has been paid to the impact on task performance of the choice of algorithm or its parameters, even for FBP or OSEM. We have developed a method, called a 'virtual clinical trial', to evaluate the ability of PET imaging to measure response to cancer therapy in a clinical trial setting. Here our goal is to determine the impact of a fully-3D PET reconstruction algorithm and parameters on clinical trial power. Methods: We performed a virtual clinical trial by generating 90 independent and identically distributed PET imaging study realizations for each of 22 original dynamic 18F-FDG breast cancer patient studies pre- and post- therapy. Each noise realization accounted for known sources of uncertainty in the imaging process, specifically biological variability and quantum noise determined by the PET scanner sensitivity and/or imaging time, as well as the trade-offs introduced by the reconstruction algorithm in bias versus variance. Results: For high quantum noise levels, due to lower PET scanner sensitivity or shorter scan times, quantum noise has a measurable effect on signal to noise ratio (SNR) and study power. However, for studies with moderate to low levels of quantum noise, biological variability and other sources of variance determine SNR and study power. In other words, the choice of the fully-3D PET reconstruction algorithm and parameters has minimal impact on task performance. Conclusions: For many clinical trials, the variance aspects of 3D PET and reconstruction method and parameters have minimal to no impact. Variance for other factors, and bias introduced by changes in 3D PET reconstruction between scans can dramatically impact the utility of clinical trials that rely on quantitative accuracy.
Blood flow-metabolism mismatch from dynamic positron emission tomography (PET) studies with O15-labeled water (H2O) and F18-labeled fluorodeoxyglucose (FDG) has been shown to be a promising diagnostic for locally advanced breast cancer (LABCa) patients. The mismatch measurement involves kinetic analysis with the arterial blood time course (AIF) as an input function. We evaluate the use of a statistical method for AIF extraction (SAIF) in these studies. Fifty three LABCa patients had dynamic PET studies with H2O and FDG. For each PET study, two AIFs were recovered, an SAIF extraction and also a manual extraction based on a region of interest placed over the left ventricle (LV-ROI). Blood flow-metabolism mismatch was obtained with each AIF, and kinetic and prognostic reliability comparisons were made. Strong correlations were found between kinetic assessments produced by both AIFs. SAIF AIFs retained the full prognostic value, for pathologic response and overall survival, of LV-ROI AIFs.
Dariya Malyarenko, Andriy Fedorov, Laura Bell, Melissa Prah, Stefanie Hectors, Lori Arlinghaus, Mark Muzi, Meiyappan Solaiyappan, Michael Jacobs, Maggie Fung, Amita Shukla-Dave, Kevin McManus, Michael Boss, Bachir Taouli, Thomas Yankeelov, Christopher Chad Quarles, Kathleen Schmainda, Thomas Chenevert, David Newitt
KEYWORDS: Diffusion weighted imaging, Diffusion, Digital imaging, Medicine, Data modeling, Data communications, MATLAB, Scanners, Standards development, Magnetic resonance imaging
This paper reports on results of a multisite collaborative project launched by the MRI subgroup of Quantitative Imaging Network to assess current capability and provide future guidelines for generating a standard parametric diffusion map Digital Imaging and Communication in Medicine (DICOM) in clinical trials that utilize quantitative diffusion-weighted imaging (DWI). Participating sites used a multivendor DWI DICOM dataset of a single phantom to generate parametric maps (PMs) of the apparent diffusion coefficient (ADC) based on two models. The results were evaluated for numerical consistency among models and true phantom ADC values, as well as for consistency of metadata with attributes required by the DICOM standards. This analysis identified missing metadata descriptive of the sources for detected numerical discrepancies among ADC models. Instead of the DICOM PM object, all sites stored ADC maps as DICOM MR objects, generally lacking designated attributes and coded terms for quantitative DWI modeling. Source-image reference, model parameters, ADC units and scale, deemed important for numerical consistency, were either missing or stored using nonstandard conventions. Guided by the identified limitations, the DICOM PM standard has been amended to include coded terms for the relevant diffusion models. Open-source software has been developed to support conversion of site-specific formats into the standard representation.
David Newitt, Dariya Malyarenko, Thomas Chenevert, C. Chad Quarles, Laura Bell, Andriy Fedorov, Fiona Fennessy, Michael Jacobs, Meiyappan Solaiyappan, Stefanie Hectors, Bachir Taouli, Mark Muzi, Paul Kinahan, Kathleen Schmainda, Melissa Prah, Erin Taber, Christopher Kroenke, Wei Huang, Lori Arlinghaus, Thomas Yankeelov, Yue Cao, Madhava Aryal, Yi-Fen Yen, Jayashree Kalpathy-Cramer, Amita Shukla-Dave, Maggie Fung, Jiachao Liang, Michael Boss, Nola Hylton
KEYWORDS: Diffusion, In vivo imaging, Diffusion weighted imaging, Breast, MATLAB, Artificial intelligence, Magnetic resonance imaging, Radiology, Statistical analysis, Medicine
Diffusion weighted MRI has become ubiquitous in many areas of medicine, including cancer diagnosis and treatment response monitoring. Reproducibility of diffusion metrics is essential for their acceptance as quantitative biomarkers in these areas. We examined the variability in the apparent diffusion coefficient (ADC) obtained from both postprocessing software implementations utilized by the NCI Quantitative Imaging Network and online scan time-generated ADC maps. Phantom and in vivo breast studies were evaluated for two (ADC2) and four (ADC4) b-value diffusion metrics. Concordance of the majority of implementations was excellent for both phantom ADC measures and in vivo ADC2, with relative biases <0.1 % (ADC2) and <0.5 % (phantom ADC4) but with higher deviations in ADC at the lowest phantom ADC values. In vivo ADC4 concordance was good, with typical biases of ±2 % to 3% but higher for online maps. Multiple b-value ADC implementations were separated into two groups determined by the fitting algorithm. Intergroup mean ADC differences ranged from negligible for phantom data to 2.8% for ADC4in vivo data. Some higher deviations were found for individual implementations and online parametric maps. Despite generally good concordance, implementation biases in ADC measures are sometimes significant and may be large enough to be of concern in multisite studies.
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