Interleaved Mapping of Temperature and Longitudinal Relaxation Rate to Monitor Drug Delivery During Magnetic Resonance–Guided High-Intensity Focused Ultrasound-Induced Hyperthermia

Abstract

The new approach of interleaving different MR sequences was applied to simultaneously acquire R1 maps and PRFS thermometry scans during a feedback-controlled MR-HIFU-induced hyperthermia treatment. Interleaved acquisition did not compromise speed or accuracy of each scan. The ΔR1 acquired during treatment was used to visualize and quantify hyperthermia-triggered release of gadoteridol from TSLs and better reflected the intratumoral doxorubicin concentrations than the ΔR1 measured after cooldown of the tumor, exemplifying the benefit of interleaving R1 maps with temperature maps during drug delivery. Our study serves as an example for interleaved MR acquisition schemes, which introduce a higher flexibility in speed, sequence optimization, and timing.

Real-time fluorescence imaging for visualization and drug uptake prediction during drug delivery by thermosensitive liposomes

“…For most human tumors, 3D imaging would be required to ensure adequate drug delivery to all regions within a deep-seated tumor volume which is not possible with fluorescence imaging. Several studies have attempted to estimate the delivered drug dose by indirect methods via co-encapsulating MRI contrast agents together with Dox that are released together with the drug (47, 33, 23), and recent studies demonstrate very good correlation between MR contrast uptake and tumor drug uptake (48) (49). The described methods are thus more directly applicable to preclinical studies with limited applicability in human tumors apart possibly from surface tumors.…”

Following nanomedicine activation with magnetic resonance imaging: why, how, and what’s next?

“…This is even more important when the pharmacokinetic profiles of the CA and the drug after release differ. The combination with other treatments or imaging modalities represents an additional practical challenge [25]. .…”

“…Moreover, the combination of heat-induced release of doxorubicin for tumor treatment and thermal ablation has been assessed, showing that the shutdown of vasculature due to ablation treatment impairs the effectiveness of drug delivery and therefore should be applied after triggering the drug release [23]. Another report addresses the challenge of simultaneous MR thermometry and T1 imaging for monitoring of CA release by introducing an interleaved scan protocol [25]. Besides manganese and gadolinium-based CAs, also an iron-complex was evaluated as a CA and the respective advantages and disadvantages were evaluated, as described later in this Opinion.…”

“…Recent publications focus on the practical execution of the MRI scan. Even though the setups for HIFU treatment under MR guidance are available, the simultaneous MR thermometry and analysis of contrast agent release remains challenging and is addressed in recent reports [25].…”

Model predictive control for MR-HIFU-mediated, uniform hyperthermia

“…In combination with MR thermometry and a simple binary feedback loop, electronic beam steering has been used to achieve MR-HIFU mediated, regional hyperthermia. The feasibility of this technique has been demonstrated in several preclinical studies [36][37][38][39][40][41][42] and recently in a first clinical trial using the MR-HIFU system Sonalleve V R (Profound Medical Inc., Toronto, Canada) [43]. By adding mechanical transducer movement facilitated by a robotic positioning system, a first large volume hyperthermia application based on MR-HIFU has been demonstrated in vivo [44] and applied clinically [45].…”