Factors Affecting the Sensitivity and Detection Limits of MRI, CT, and SPECT for Multimodal Diagnostic and Therapeutic Agents

Abstract

Noninvasive imaging techniques like magnetic resonance imaging (MRI), computed tomography (CT) and single photon emission computed tomography (SPECT) play an increasingly important role in the diagnostic workup and treatment of cancerous disease. In this context, a distinct trend can be observed towards the development of contrast agents and radiopharmaceuticals that open up perspectives on a multimodality imaging approach, involving all three aforementioned techniques. To promote insight into the potentialities of such an approach, we prepared an overview of the strengths and limitations of the various imaging techniques, in particular with regard to their capability to quantify the spatial distribution of a multimodal diagnostic agent. To accomplish this task, we used a two-step approach. In the first step, we examined the situation for a particular therapeutic anti-cancer agent with multimodal imaging opportunities, viz. holmium-loaded microspheres (HoMS). Physical phantom experiments were performed to enable a comparative evaluation of the three modalities assuming the use of standard equipment, standard clinical scan protocols, and signal-known-exactly conditions. These phantom data were then analyzed so as to obtain first order estimates of the sensitivity and detection limits of MRI, CT and SPECT for HoMS. In the second step, the results for HoMS were taken as a starting point for a discussion of the factors affecting the sensitivity and detection limits of MRI, CT and SPECT for multimodal agents in general. In this, emphasis was put on the factors that must be taken into account when extrapolating the findings for HoMS to other diagnostic tasks, other contrast agents, other experimental conditions, and other scan protocols.

Safety of a Scout Dose Preceding Hepatic Radioembolization with 166Ho Microspheres

“…Although spatial resolution, contrast recovery, and sensitivity are worse for 166 Ho than 99m Tc-MAA, injection of 250 MBq of 166 Ho microspheres is sufficient to provide images that allow for the evaluation of lung shunt and extrahepatic deposition (24,25). Another benefit of 166 Ho microspheres, and a principal reason for their development (26), is the possibility of their multimodal detection: an 81-keV photopeak for nuclear imaging (24), high magnetic susceptibility for MR imaging (27), and a high mass attenuation coefficient for CT imaging (28). The most promising modality, MR imaging, could enable MR-guided treatment, as has been performed ex vivo in rabbits (29).…”

Microspheres with Ultrahigh Holmium Content for Radioablation of Malignancies

“…Quantitative CT of the agarose phantom resulted in a mass attenuation coefficient at 120 kV of 15.6 HU mg −1 ml for HoAcAc MS, which is substantially increased, when compared to the mass attenuation coefficient of HoPLLA microspheres of 6.7 HU mg −1 ml at 120 kV (14). This increase in CT sensitivity, like the increase of sensitivity of MRI to the HoAcAc microspheres, can be attributed to the increase in holmium content.…”

“…Monoexponential signal decay was assumed. Data processing was performed as described by Seevinck et al (14). A second agarose gel phantom was constructed for qualitative imaging.…”

“…The sample tubes were positioned co-axially to the main axis of the scanner. Using the methods described by Seevinck et al, a linear regression curve was constructed to determine the sensitivity of X-ray CT for HoAcAc microspheres (14).…”

“…The lack of (quantitative) imaging options for 90 Y (9) has lead to the development of holmium-166 loaded poly(L-lactic acid) ( 166 HoPLLA) microspheres, since 166 Ho emits gamma rays and beta particles that can be used for nuclear imaging and therapy, respectively (10)(11)(12). Moreover, holmium is highly paramagnetic and has a high linear attenuation coefficient allowing for visualization by magnetic resonance imaging (MRI) and X-ray computed tomography (CT), respectively (13,14).…”