Breast imaging with an ultra-low field MRI scanner: a pilot study.

Breast cancer screening is necessary to reduce mortality due to undetected breast cancer. Current methods have limitations, and as a result many women forego regular screening. Magnetic resonance imaging (MRI) can overcome most of these limitations, but access to conventional MRI is not widely available for routine annual screening. Here, we used an MRI scanner operating at ultra-low field (ULF) to image the left breasts of 11 women (mean age, 35 years ±13 years) in the prone position. Three breast radiologists reviewed the imaging and were able to discern the breast outline and distinguish fibroglandular tissue (FGT) from intramammary adipose tissue. Additionally, the expert readers agreed on their assessment of the breast tissue pattern including fatty, scattered FGT, heterogeneous FGT, and extreme FGT. This preliminary work demonstrates that ULF breast MRI is feasible and may be a potential option for comfortable, widely deployable, and low-cost breast cancer diagnosis and screening.

Real-time radial reconstruction with domain transform manifold learning for MRI-guided radiotherapy.

BACKGROUND: MRI-guidance techniques that dynamically adapt radiation beams to follow tumor motion in real time will lead to more accurate cancer treatments and reduced collateral healthy tissue damage. The gold-standard for reconstruction of undersampled MR data is compressed sensing (CS) which is computationally slow and limits the rate that images can be available for real-time adaptation. PURPOSE: Once trained, neural networks can be used to accurately reconstruct raw MRI data with minimal latency. Here, we test the suitability of deep-learning-based image reconstruction for real-time tracking applications on MRI-Linacs. METHODS: We use automated transform by manifold approximation (AUTOMAP), a generalized framework that maps raw MR signal to the target image domain, to rapidly reconstruct images from undersampled radial k-space data. The AUTOMAP neural network was trained to reconstruct images from a golden-angle radial acquisition, a benchmark for motion-sensitive imaging, on lung cancer patient data and generic images from ImageNet. Model training was subsequently augmented with motion-encoded k-space data derived from videos in the YouTube-8M dataset to encourage motion robust reconstruction. RESULTS: AUTOMAP models fine-tuned on retrospectively acquired lung cancer patient data reconstructed radial k-space with equivalent accuracy to CS but with much shorter processing times. Validation of motion-trained models with a virtual dynamic lung tumor phantom showed that the generalized motion properties learned from YouTube lead to improved target tracking accuracy. CONCLUSION: AUTOMAP can achieve real-time, accurate reconstruction of radial data. These findings imply that neural-network-based reconstruction is potentially superior to alternative approaches for real-time image guidance applications.

In vivo MEMRI characterization of brain metastases using a 3D Look-Locker T1-mapping sequence.

Although MEMRI (Manganese Enhanced MRI) informations were obtained on primary tumors in small animals, MEMRI data on metastases are lacking. Thus, our goal was to determine if 3D Look-Locker T1 mapping was an efficient method to evaluate Mn ions transport in brain metastases in vivo. The high spatial resolution in 3D (156 × 156 × 218 µm) of the sequence enabled to detect metastases of 0.3 mm3. In parallel, the T1 quantitation enabled to distinguish three populations of MDA-MB-231 derived brain metastases after MnCl2 intravenous injection: one with a healthy blood-tumor barrier that did not internalize Mn2+ ions, and two others, which T1 shortened drastically by 54.2% or 24%. Subsequent scans of the mice, enabled by the fast acquisition (23 min), demonstrated that these T1 reached back their pre-injection values in 24 h. Contrarily to metastases, the T1 of U87-MG glioma remained 26.2% shorter for one week. In vitro results supported the involvement of the Transient Receptor Potential channels and the Calcium-Sensing Receptor in the uptake and efflux of Mn2+ ions, respectively. This study highlights the ability of the 3D Look-Locker T1 mapping sequence to study heterogeneities (i) amongst brain metastases and (ii) between metastases and glioma regarding Mn transport.

Alkoxyamines: toward a new family of theranostic agents against cancer.

Theranostics combines therapeutic and diagnostic or drug deposition monitoring abilities of suitable molecules. Here we describe the first steps of building an alkoxyamine-based theranostic agent against cancer. The labile alkoxyamine ALK-1 (t(1/2) = 50 min at 37 °C) cleaves spontaneously to generate (1) a highly reactive free alkyl radical used as therapeutic agents to induce cell damages leading to cell death and (2) a stable nitroxide used as contrast agent for Overhauser-enhanced magnetic resonance imaging (OMRI). The ALK-1 toxicity was studied extensively in vitro on the glioblastoma cell line U87-MG. Cell viability appeared to be dependent on ALK-1 concentration and on the time of the observation following alkoxyamine treatment. For instance, the LC50 at 72 h was 250 µM. Data showed that cell toxicity was specifically due to the in situ released alkyl radical. This radical induced oxidative stress, mitochondrial changes, and ultimately the U87 cell apoptosis. The nitroxide production, during the alkoxyamine homolysis, was monitored by OMRI, showing a progressive MRI signal enhancement to 6-fold concomitant to the ALK-1 homolysis. In conclusion, we have demonstrated for the first time that the alkoxyamines are promising molecules to build theranostic tools against solid tumors.

Overhauser-enhanced MRI of elastase activity from in vitro human neutrophil degranulation.

BACKGROUND: Magnetic resonance imaging can reveal exquisite anatomical details. However several diseases would benefit from an imaging technique able to specifically detect biochemical alterations. In this context protease activity imaging is one of the most promising areas of research. METHODOLOGY/PRINCIPAL FINDINGS: We designed an elastase substrate by grafting stable nitroxide free radicals on soluble elastin. This substrate generates a high Overhauser magnetic resonance imaging (OMRI) contrast upon digestion by the target proteases through the modulation of its rotational correlation time. The sensitivity is sufficient to generate contrasted images of the degranulation of neutrophils induced by a calcium ionophore from 2×10(4) cells per milliliter, well under the physiological neutrophils concentrations. CONCLUSIONS/SIGNIFICANCE: These ex-vivo experiments give evidence that OMRI is suitable for imaging elastase activity from neutrophil degranulation. Provided that a fast protease-substrate is used these results open the door to better diagnoses of a number of important pathologies (cystic fibrosis, inflammation, pancreatitis) by OMRI or Electron Paramagnetic Resonance Imaging in vivo. It also provides a long-expected method to monitor anti-protease treatments efficiency and help pharmaceutical research.