51 research outputs found
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High contrast dual-mode optical and 13C magnetic resonance imaging in diamond particles
Multichannel imaging -- the ability to acquire images of an object through
more than one imaging mode simultaneously -- has opened interesting new
perspectives in areas ranging from astronomy to medicine. Visible optics and
magnetic resonance imaging (MRI) offer complementary advantages of resolution,
speed and depth of penetration, and as such would be attractive in combination.
In this paper, we take first steps towards marrying together optical and MR
imaging in a class of biocompatible particulate materials constructed out of
diamond. The particles are endowed with a high density of quantum defects
(Nitrogen Vacancy centers) that under optical excitation fluoresce brightly in
the visible, but also concurrently electron spin polarize. This allows the
hyperpolarization of lattice 13C nuclei to make the particles over three-orders
of magnitude brighter than in conventional MRI. Dual-mode optical and MR
imaging permits immediate access to improvements in resolution and
signal-to-noise especially in scattering environments. We highlight additional
benefits in background-free imaging, demonstrating lock-in suppression by
factors of 2 and 5 in optical and MR domains respectively. Ultimate limits
could approach as much as two orders of magnitude in each domain. Finally,
leveraging the ability of optical and MR imaging to simultaneously probe
Fourier-reciprocal domains (real and k-space), we elucidate the ability to
employ hybrid sub-sampling in both conjugate spaces to vastly accelerate
dual-image acquisition, by as much as two orders of magnitude in practically
relevant sparse-imaging scenarios. This is accompanied by a reduction in
optical power by the same factor. Our work suggests interesting possibilities
for the simultaneous optical and low-field MR imaging of targeted diamond
nanoparticles
Modulators of Prostate Cancer Cell Proliferation and Viability Identified by Short-Hairpin RNA Library Screening
There is significant need to identify novel prostate cancer drug targets because current hormone therapies eventually fail, leading to a drug-resistant and fatal disease termed castration-resistant prostate cancer. To functionally identify genes that, when silenced, decrease prostate cancer cell proliferation or induce cell death in combination with antiandrogens, we employed an RNA interference-based short hairpin RNA barcode screen in LNCaP human prostate cancer cells. We identified and validated four candidate genes (AKT1, PSMC1, STRADA, and TTK) that impaired growth when silenced in androgen receptor positive prostate cancer cells and enhanced the antiproliferative effects of antiandrogens. Inhibition of AKT with a pharmacologic inhibitor also induced apoptosis when combined with antiandrogens, consistent with recent evidence for PI3K and AR pathway crosstalk in prostate cancer cells. Recovery of hairpins targeting a known prostate cancer pathway validates the utility of shRNA library screening in prostate cancer as a broad strategy to identify new candidate drug targets
Is autoimmunity the Achilles' heel of cancer immunotherapy?
The emergence of immuno-oncology as the first broadly successful strategy for metastatic cancer will require clinicians to integrate this new pillar of medicine with chemotherapy, radiation, and targeted small-molecule compounds. Of equal importance is gaining an understanding of the limitations and toxicities of immunotherapy. Immunotherapy was initially perceived to be a relatively less toxic approach to cancer treatment than other available therapies-and surely it is, when compared to those. However, as the use of immunotherapy becomes more common, especially as first- and second-line treatments, immunotoxicity and autoimmunity are emerging as the Achilles' heel of immunotherapy. In this Perspective, we discuss evidence that the occurrence of immunotoxicity bodes well for the patient, and describe mechanisms that might be related to the induction of autoimmunity. We then explore approaches to limit immunotoxicity, and discuss the future directions of research and reporting that are needed to diminish it
Multi-reception strategy with improved SNR for multichannel MR imaging
A multi-reception strategy with extended GRAPPA is proposed in this work to improve MR imaging performance at ultra-high field MR systems with limited receiver channels. In this method, coil elements are separated to two or more groups under appropriate g
Tilted microstrip phased arrays with improved electromagnetic decoupling for ultrahigh-field magnetic resonance imaging
Copyright Β© 2014 Wolters Kluwer Health / Lippincott Williams & Wilkins.One of the technical challenges in designing a dedicated transceiver radio frequency (RF) array for MR imaging in humans at ultrahigh magnetic fields is how to effectively decouple th
Design of spectral-spatial outer volume suppression RF pulses for tissue specific metabolic characterization with hyperpolarized 13C pyruvate.
[1-(13)C] pyruvate pre-polarized via DNP has been used in animal models to probe changes in metabolic enzyme activities in vivo. To more accurately assess the metabolic state and its change from disease progression or therapy in a specific region or tissue in vivo, it may be desirable to separate the downstream (13)C metabolite signals resulting from the metabolic activity within the tissue of interest and those brought into the tissue by perfusion. In this study, a spectral-spatial saturation pulse that selectively saturates the signal from the metabolic products [1-(13)C] lactate and [1-(13)C] alanine was designed and implemented as outer volume suppression for localized MRSI acquisition. Preliminary in vivo results showed that the suppression pulse did not prevent the pre-polarized pyruvate from being delivered throughout the animal while it saturated the metabolites within the targeted saturation region
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The role of metabolic imaging in radiation therapy of prostate cancer.
The goal of this study was to correlate prostatic metabolite concentrations from snap-frozen patient biopsies of recurrent cancer after failed radiation therapy with histopathological findings, including Ki-67 immunohistochemistry and pathologic grade, in order to identify quantitative metabolic biomarkers that predict for residual aggressive versus indolent cancer. A total of 124 snap-frozen transrectal ultrasound (TRUS)-guided biopsies were acquired from 47 men with untreated prostate cancer and from 39 men with a rising prostate-specific antigen and recurrent prostate cancer following radiation therapy. Biopsy tissues with Ki-67 labeling index β€ 5% were classified as indolent cancer, while biopsy tissues with Ki-67 labeling index > 5% were classified as aggressive cancer. The majority (15 out of 17) of cancers classified as aggressive had a primary Gleason 4 pattern (Gleason score β₯ 4 + 3). The concentrations of choline-containing phospholipid metabolites (PC, GPC, and free Cho) and lactate were significantly elevated in recurrent cancer relative to surrounding benign tissues. There was also a significant increase in [PC] and reduction in [GPC] between untreated and irradiated prostate cancer biopsies. The concentration of the choline-containing phospholipid metabolites was significantly higher in recurrent aggressive (β twofold) than in recurrent indolent cancer biopsies, and the receiver operating characteristic (ROC) curve analysis of total choline to creatine ratio (tCho/Cr) demonstrated an accuracy of 95% (confidence interval = 0.88-1.00) for predicting aggressive recurrent disease. The tCho/Cr was significantly higher for identifying recurrent aggressive versus indolent cancer (tCho/Cr = 2.4 Β± 0.4 versus 1.5 Β± 0.2), suggesting that use of a higher threshold tCho/Cr ratio in future in vivo (1)H MRSI studies could improve the selection and therapeutic planning for patients who would benefit most from salvage focal therapy after failed radiation therapy
The role of metabolic imaging in radiation therapy of prostate cancer.
The goal of this study was to correlate prostatic metabolite concentrations from snap-frozen patient biopsies of recurrent cancer after failed radiation therapy with histopathological findings, including Ki-67 immunohistochemistry and pathologic grade, in order to identify quantitative metabolic biomarkers that predict for residual aggressive versus indolent cancer. A total of 124 snap-frozen transrectal ultrasound (TRUS)-guided biopsies were acquired from 47 men with untreated prostate cancer and from 39 men with a rising prostate-specific antigen and recurrent prostate cancer following radiation therapy. Biopsy tissues with Ki-67 labeling index β€ 5% were classified as indolent cancer, while biopsy tissues with Ki-67 labeling index > 5% were classified as aggressive cancer. The majority (15 out of 17) of cancers classified as aggressive had a primary Gleason 4 pattern (Gleason score β₯ 4 + 3). The concentrations of choline-containing phospholipid metabolites (PC, GPC, and free Cho) and lactate were significantly elevated in recurrent cancer relative to surrounding benign tissues. There was also a significant increase in [PC] and reduction in [GPC] between untreated and irradiated prostate cancer biopsies. The concentration of the choline-containing phospholipid metabolites was significantly higher in recurrent aggressive (β twofold) than in recurrent indolent cancer biopsies, and the receiver operating characteristic (ROC) curve analysis of total choline to creatine ratio (tCho/Cr) demonstrated an accuracy of 95% (confidence interval = 0.88-1.00) for predicting aggressive recurrent disease. The tCho/Cr was significantly higher for identifying recurrent aggressive versus indolent cancer (tCho/Cr = 2.4 Β± 0.4 versus 1.5 Β± 0.2), suggesting that use of a higher threshold tCho/Cr ratio in future in vivo (1)H MRSI studies could improve the selection and therapeutic planning for patients who would benefit most from salvage focal therapy after failed radiation therapy
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