This is the final article in a series of three providing a primer for radiologists and imaging professionals interested in clinical trials.
Over the past two decades, there has been a significant evolution in the methodology of clinical trials, specifically as it applies to the use of medical imaging as a surrogate endpoint or biomarker. While the use of medical imaging has now garnered mainstream acceptance in clinical-trial arenas to make trials more effective and accurate, the actual use of imaging in trials remains in its infancy.
In order to satisfy regulatory requirements and access the most widely available technology, imaging contract-research organizations (CROs) have primarily advocated the use of conventional modalities and methods, as they are easily translatable from the clinical sphere to research protocols. As mainstream acceptance has widened, however, investigators have begun to look into new modalities, newer protocols, and new methods for using medical imaging in clinical trials.
As most current clinical trials involve oncology, the workhorse modalities are CT and MRI (due to the validation and acceptance of response-evaluation criteria in solid tumors). CT technology has evolved to allow isometric voxel imaging and reproducible 3D imaging, and MRI allows evaluation of a broad range of imaging elements, from metabolism and physiology to tissue microstructure.
CT: The main developments in CT have been related to the introduction of multidetector spiral CT. Multidetector imaging allows multiplanar and 3D rendering of anatomical structures with a level of detail that is on par with that of other planar modalities—conventional angiography, for example, when compared with CT angiography.
The evolution of CT technology has produced improvements in multiple areas, including better spatial resolution, reduced radiation dose, in-vivo high-resolution CT imaging, flat-panel–detector CT, and dual-energy CT. As these technologies are vetted and gain acceptance in clinical practice, they will become involved in protocols for trial imaging.
MRI: The evolution of MRI technology has seen the use of both 1.5T and 3T magnets become conventional. For body applications, while 1.5T remains the current standard, the benefits of increased resolution at 3T ultimately will translate to trial imaging. The exquisite imaging obtained on 3T units for neuroimaging and the reproducibility available for cardiac imaging have already caused 3T MRI to make its way into limited clinical trials.
Ultrahigh-field (7T) imaging systems are currently in research use, typically for neuroimaging applications, but these are unlikely to find acceptance as a clinical technology (and, consequently, in clinical trials) due to their high overhead and limited scope of utility for clinical applications.
Since the introduction of multichannel coils, eight and 16-channel devices have become increasingly common, and modern systems are designed to accommodate upgrades to 24 or 32 channels (or more). Devices that are specific to laboratory research have been taken up to 100 channels. The higher-channel devices allow research protocols to focus on specific organs or specific disease processes, permitting imaging charters to be more precise in the impact of drugs being studied.
Integrated modalities: These (especially PET/CT and PET/MRI) are a particular focus for oncology applications. While PET, as a stand-alone modality, has been validated for use in clinical trials, radiologists have limited its use primarily to diagnosis (due to the lack of anatomical data). Integrating PET and CT provides the anatomical detail that helps imaging CROs to decrease the level of adjudication required across time points.
Manufacturers have surmounted incredible challenges in coupling the high magnetic fields of the MRI magnets with PET equipment. As this challenge is overcome, PET/MRI will make the natural progression from the clinical sphere to trial methodology, promoting a more accurate understanding of the relationship of metabolic and structural data through a higher spatial resolution than is possible with PET/CT.
Improvements in software relate primarily to management of trials and trial imaging. This field also has witnessed an explosion in the use of software, on dedicated workstations, that allows improved visualization of imaging data.
Trial-management software: Clinical trials were once managed using stand-alone, proprietary