One solution may lie in magnetic particle imaging (MPI), an emerging modality that images superparamagnetic iron oxide (SPIO) nanoparticles inside the body. MPI benefits from high sensitivity, rapid image acquisition, sub-millimetre resolution and zero ionizing radiation. The injected nanoparticles can also be tracked over long time scales. Now, a research team headed up at UC Berkeley has demonstrated the first use of MPI to visualize brain injury in vivo (Phys. Med. Biol. 62 3501).

"Traumatic brain injury is challenging to diagnose properly due to the qualitative nature of the behavioural tests used in TBI assessments," explains first author Ryan Orendorff from the Berkeley Imaging Systems Laboratory. "MPI has been shown in several papers to be an excellent modality for imaging pooling blood. As such, we were keen to evaluate the ability of MPI to image TBI events where fluid can leak into the interstitial cranial space from the blood vasculature."

How MPI works

SPIO particles have a nonlinear magnetization response to an applied magnetic field: when the field is low, the particles respond approximately linearly; but at larger field strengths, particle response saturates as nearly all particles are aligned with the applied field. MPI exploits this saturation phenomenon to image only a small number of particles within a volume.

MPI scanners use two opposed permanent magnets to create a magnetic field gradient with a field free region (FFR) in the centre. This arrangement allows particles inside the FFR to respond linearly to an applied field, while particles outside of the FFR experience a saturating applied field, and thereby produce no signal. The scanner creates an image by rastering the FFR over space to acquire signal from SPIOs at each point.

In vivo investigations

Orendorff and colleagues used MPI to image two anaesthetised rats, one of which had sustained a moderate closed-skull TBI. Scans were performed with a 4.0 x 3.75 x 8.5 cm field-of-view and an acquisition time of roughly 10 minutes. The animals were injected with LS-13 SPIO particles (from LodeSpin Labs), which offer an image resolution of approximately 2 mm.

MPI scans clearly showed signal in the brain region affected by the TBI, indicating that bleeding was significant enough to allow SPIO particles to infiltrate into the interstitial space. The signal caused by the injury was observed both immediately following the impact and a few days later. In the non-injured animal, no signal above noise level was detected in the equivalent brain area.

The images indicated that SPIOs accumulated rapidly after impact and persisted for two weeks. The half-life of the particle signal in the impact region was approximately four days – demonstrating a significantly retarded clearance rate from the estimated six hour blood half-life of LS-13 particles.

In both animals, signal also accumulated in small regions on both sides in the neck (thought to be the lymph nodes) after approximately half a day. The clearance half-life for the control animal was three days, while the TBI animal experienced a slightly delayed clearance of four days.

This ability to image haemorrhages makes MPI a potential augmentation or replacement for CT in clinical settings. Imaging mild to medium severity injuries with CT remains a challenge, partly because the signal of interest may be obscured by signal from background tissues. As MPI does not detect background tissues (only the administered iron particles produce a signal), it creates images with excellent contrast-to-noise ratio.

Orendorff and colleagues are now working on novel reconstruction methods for MPI, focusing on how to best utilize every bit of data recorded during an MPI scanning session. "This work will enable real time and interactive imaging in high-resolution MPI scanners," Orendorff explains.

This study was a multi-team effort spanning many institutions, including the Kaufer and Brooks Labs at UC Berkeley, the Kannon Lab at University of Washington and LodeSpin Labs in Washington. Funding was provided by the NIH, Keck Foundation and NSF GRFP. This paper is a direct result of the dedicated effort of all of these teams towards enabling TBI imaging through MPI.

• This paper is part of a Physics in Medicine & Biology special issue: Recent progress in magnetic particle imaging: from engineering to preclinical applications.

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