Application of Trifluoroacetic Acid as a Theranostic Agent for Chemical Ablation of Solid Tissue.

PURPOSE: To evaluate trifluoroacetic acid (TFA) as a theranostic chemical ablation agent and determine the efficacy of TFA for both noninvasive imaging and tissue destruction. MATERIALS AND METHODS: Fluorine-19 magnetic resonance imaging (19F-MRI) was optimized at 7 T using a custom-built volume coil. Fluorine images were acquired with both rapid acquisition with relaxation enhancement and balanced steady-state free precession (bSSFP) sequences with varying parameters to determine the optimal sequence for TFA. The theranostic efficacy of chemical ablation was examined by injecting TFA (100 µL; 0.25, 0.5, 1.0, and 2.0M) into ex vivo porcine liver. 19F and proton MRI were acquired and superimposed to visualize distribution of TFA in tissue and quantify sensitivity. Tissue damage was evaluated with gross examination, histology, and fluorescence microscopy. RESULTS: The optimal 19F-MRI sequence was found to be bSSFP with a repetition time of 2.5 ms and flip angle of 70°. The minimum imageable TFA concentration was determined to be 6.7 ± 0.5 mM per minute of scan time (0.63×0.63×5.00 mm voxel), and real-time imaging (temporal resolution of at least 1 s-1) was achieved with 2M TFA both in vitro and in ex vivo tissue. TFA successfully coagulated tissue, and damage was locally confined. In addition to hepatic cord disruption, cytoskeletal collapse and chromatin clumping were observed in severely damaged areas in tissues treated with 0.5M or higher TFA concentrations. CONCLUSIONS: TFA was determined to be a theranostic agent for chemical ablation of solid tissue. Ablation was both efficacious and imageable in ex vivo healthy tissue, even at low concentrations or with high temporal resolution.

Quantification and homogenization of image noise between two CT scanner models.

Feedback from radiologists indicated that differences in image appearance and noise impeded reading of post-contrast computed tomography (CT) scans from an updated CT scanner that was recently added to a fleet of existing scanners from the same vendor, despite using identically named reconstruction algorithms. The goals of this work were to quantify and possibly standardize image quality on the new and an existing scanner using phantom images. Three months of daily quality control images were analyzed to determine the mean CT number and noise magnitude in a water phantom. Next, subtraction images from the uniformity section of an American College of Radiology CT phantom were used to generate noise power spectra for both scanners. Then, a semi-anthropomorphic liver phantom was imaged with both scanners in triplicate using identical body protocols to quantify differences CT number and noise magnitude. Finally, the scanner dependence of CT number and noise magnitude on material attenuation was quantified using a multi-energy CT phantom with 15 material inserts. Significant differences between scanners were determined using a paired or Welch's t test as appropriate. In daily quality control images, the new scanner exhibited slightly higher CT number (0.697 vs. 0.412, P < 0.001, n = 85) and slightly lower noise magnitude (4.85 vs. 4.94, P < 0.001, n = 85). Measured NPS was not significantly different between the existing and new scanners. Interestingly, it was observed that the noise magnitude from the new scanner increased with increasing material attenuation in both the liver (P = 0.008) and multi-energy (P < 0.001) phantoms. Using an alternate reconstruction algorithm with the new scanner eliminated this deviation at high material attenuations. While standard noise evaluation in a water phantom was unable to discern differences between the scanners, more comprehensive testing with higher attenuation materials allowed for the characterization and homogenization of image quality.

Correction to: Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI.

There was a typo in author Andrew Wahba's name in the initial online publication. The original article has been corrected.

Monitoring of intracerebellarly-administered natural killer cells with fluorine-19 MRI.

PURPOSE: Medulloblastoma (MB) is the most common malignant brain tumor in children. Recent studies have shown the ability of natural killer (NK) cells to lyse MB cell lines in vitro, but in vivo successes remain elusive and the efficacy and fate of NK cells in vivo remain unknown. METHODS: To address these questions, we injected MB cells into the cerebellum of immunodeficient mice and examined tumor growth at various days after tumor establishment via bioluminescence imaging. NK cells were labeled with a fluorine-19 (19F) MRI probe and subsequently injected either intratumorally or contralaterally to the tumor in the cerebellum and effect on tumor growth was monitored. RESULTS: The 19F probe efficiently labeled the NK cells and exhibited little cytotoxicity. Fluorine-19 MRI confirmed the successful and accurate delivery of the labeled NK cells to the cerebellum of the mice. Administration of 19F-labeled NK cells suppressed MB growth, with the same efficacy as unlabeled cells. Immunohistochemistry confirmed the presence of NK cells within the tumor, which was associated with induction of apoptosis in tumor cells. NK cell migration to the tumor from a distal location as well as activation of apoptosis was also demonstrated by immunohstochemistry. CONCLUSIONS: Our results show that NK cells present a novel opportunity for new strategies in MB treatment. Further, 19F-labeled NK cells can suppress MB growth while enabling 19F MRI to provide imaging feedback that can facilitate study and optimization of therapeutic paradigms.

Artifacts in Digital Breast Tomosynthesis.

OBJECTIVE: Artifacts in digital breast tomosynthesis and synthesized 2D imaging reduce image quality. This article describes the appearance of these unique artifacts, reviews their causes, and discusses methods to ameliorate these artifacts. CONCLUSION: Artifacts in digital breast tomosynthesis and synthesized 2D imaging can obscure important findings on mammograms. The radiologist, mammography technologist, and medical physicist must be able to recognize these artifacts and use the vendor's new processing algorithms to mitigate the effects of such artifacts.

Noninvasive assessment of tissue-engineered graft viability by oxygen-17 magnetic resonance spectroscopy.

Transplantation of macroencapsulated tissue-engineered grafts (TEGs) is being investigated as a treatment for type 1 diabetes, but there is a critical need to measure TEG viability both in vitro and in vivo. Oxygen deficiency is the most critical issue preventing widespread implementation of TEG transplantation and delivery of supplemental oxygen (DSO) has been shown to enhance TEG survival and function in vivo. In this study, we demonstrate the first use of oxygen-17 magnetic resonance spectroscopy (17 O-MRS) to measure the oxygen consumption rate (OCR) of TEGs and show that in addition to providing therapeutic benefits to TEGs, DSO with 17 O2 can also enable measurements of TEG viability. Macroencapsulated TEGs containing ßTC3 murine insulinoma cells were prepared with three fractional viabilities and provided with 17 O2 . Cellular metabolism of 17 O2 into nascent mitochondrial water (H217 O) was monitored by 17 O-MRS and, from the measured data, OCR was calculated. For comparison, OCR was simultaneously measured on a separate, but equivalent sample of cells with a well-established stirred microchamber technique. OCR measured by 17 O-MRS agreed well with measurements made in the stirred microchamber device. These studies confirm that 17 O-MRS can quantify TEG viability noninvasively. Biotechnol. Bioeng. 2017;114: 1118-1121. © 2016 Wiley Periodicals, Inc.

Synthesis of Intrinsically Disordered Fluorinated Peptides for Modular Design of High-Signal 19 F MRI Agents.

19 F MRI is valuable for in vivo imaging due to the only trace amounts of fluorine in biological systems. Because of the low sensitivity of MRI however, designing new fluorochemicals remains a significant challenge for achieving sufficient 19 F signal. Here, we describe a new class of high-signal, water-soluble fluorochemicals as 19 F MRI imaging agents. A polyamide backbone is used for tuning the proteolytic stability to avoid retention within the body, which is a limitation of current state-of-the-art perfluorochemicals. We show that unstructured peptides containing alternating N-ϵ-trifluoroacetyllysine and lysine provide a degenerate 19 F NMR signal. 19 F MRI phantom images provide sufficient contrast at micromolar concentrations, showing promise for eventual clinical applications. Finally, the degenerate high signal characteristics were retained when conjugated to a large protein, indicating potential for in vivo targeting applications, including molecular imaging and cell tracking.

Building Radiology Equity: Themes from the 2023 RAD-AID Conference on International Radiology and Global Health.

Low- and middle-income countries are significantly impacted by the global scarcity of medical imaging services. Medical imaging is an essential component for diagnosis and guided treatment, which is needed to meet the current challenges of increasing chronic diseases and preparedness for acute-care response. We present some key themes essential for improving global health equity, which were discussed at the 2023 RAD-AID Conference on International Radiology and Global Health. They include (1) capacity building, (2) artificial intelligence, (3) community-based patient navigation, (4) organizational design for multidisciplinary global health strategy, (5) implementation science, and (6) innovation. Although not exhaustive, these themes should be considered influential as we guide and expand global health radiology programs in low- and middle-income countries in the coming years.

Correction and optimization of symmetric echo-planar spectroscopic imaging for hyperpolarized [1-13C]-pyruvate.

Symmetric echo-planar spectroscopic imaging (EPSI) supports higher spectral bandwidth and improves signal-to-noise efficiency compared to flyback EPSI with the same readout bandwidth, but suffers from artifacts that are associated with non-uniform temporal sampling in k-t space. Our goal is to eliminate these artifacts and enhance observation of hyperpolarized [1-13C] pyruvate and its metabolites using symmetric EPSI. We used symmetric EPSI to efficiently acquire radially encoded spectroscopic imaging projections with a spectral under-sampling scheme that was optimized for HP pyruvate and its metabolites. A simple approach called selective correction of off-resonance effects (SCORE) was developed and applied to eliminate spectral artifacts. Simulations were used to assess the relative SNR performance of this technique, and a phantom study was carried out at 3 T to evaluate this method and compare it with alternative strategies. SCORE correction eliminated spectral artifacts due to chemical shift and non-uniform sampling in time. It is also compatible with established methods to eliminate artifacts caused by eddy currents. SCORE corrected symmetric EPSI supported maximal EPSI spectral bandwidth and improved SNR efficiency. Symmetric EPSI with SCORE correction offers a straightforward, efficient, and effective framework for assessment of hyperpolarized [1-13C] pyruvate and its metabolites.

Noninvasive Fluorine-19 Magnetic Resonance Relaxometry Measurement of the Partial Pressure of Oxygen in Acellular Perfluorochemical-loaded Alginate Microcapsules Implanted in the Peritoneal Cavity of Nonhuman Primates.

BACKGROUND: We have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally in healthy nonhuman primates (NHPs). Average pO2 is important for determining if a transplant site and capsules with certain passive diffusion characteristics can support the islet viability, metabolic activity, and dose necessary to reverse diabetes. METHODS: Perfluoro-15-crown-5-ether alginate capsules were infused intraperitoneally into 3 healthy NHPs. Peritoneal pO2 levels were measured on days 0 and 7 using fluorine-19 magnetic resonance relaxometry and a fiber-optic probe. Fluorine-19 MRI was used to determine the locations of capsules within the peritoneal space on days 0 and 7. Gross and histologic evaluations of the capsules were used to assess their biocompatibility postmortem. RESULTS: At day 0 immediately after infusion of capsules equilibrated to room air, capsules were concentrated near the infusion site, and the pO2 measurement using magnetic resonance relaxometry was 147 ± 9 mm Hg. On day 7 after capsules were dispersed throughout the peritoneal cavity, the pO2 level was 61 ± 11 mm Hg. Measurements using the fiber-optic oxygen sensor were 132 ± 7.5 mm Hg (day 0) and 89 ± 6.1 mm Hg (day 7). Perfluoro-15-crown-5-ether capsules retrieved on day 7 were intact and free-floating without host cell attachment, although the numbers of peritoneal CD20 B cells, CD4 and CD8 T cells, and CD14 macrophages increased consistent with a mild foreign body reaction. CONCLUSIONS: The peritoneal pO2 of normal NHPs is relatively low and we predict would decrease further when encapsulated islets are transplanted intraperitoneally.

Impact of free-breathing CT on quantitative measurements of static and quiescent period-gated PET Images.

Measurements of standardized uptake values (SUV) can vary due to many causes, including respiratory motion. Various methodologies have been introduced to correct for motion in PET, with quiescent-period-gated (QPG) PET being the most popular approach. QPG has been shown to improve PET image quantification compared to static-whole-body (SWB) PET. However, to achieve this improvement, QPG PET requires CT attenuation correction data that matches the QPG PET data. In this paper we investigated the effect of using free-breathing CT for attenuation correction of QPG PET on SUVmax and SUVpeak and compared the results to those of SWB PET. 34 lesions in 27 patients were included. All patients were injected with F-18 FDG. 4D-CT datasets representing all possible phases of respiration that could result from a free-breathing CT were acquired. The 4D-CT datasets were used for attenuation correction of the QPG and SWB PET data. Percentage change in the SUVmax and SUVpeak range was calculated for the reconstructions and compared between QPG and SWB PET. The mean percentage change in the lesion SUVmax and SUVpeak ranges were 19.1% (p  = 0.0178) and 25.2% (p  = 0.0002) higher for QPG compared to SWB, respectively. The maximum percent change in SUVmax and SUVpeak ranges were 58.5% and 59.0% for QPG, respectively compared to 46.1% and 45.3% for SWB, respectively. The highest SUVmax and SUVpeak measurements corresponded to the CT phase that matched the QPG phase. Utilizing free-breathing CT for attenuation correction can lead to large changes in quantification due to misalignment with PET data. This misalignment has a large quantitative impact on QPG PET as compared to SWB PET. When interpreting quantitative changes in lesions, it is critical to consider the influences of free-breathing CT-based attenuation correction.

Performance evaluation of the 5-Ring GE Discovery MI PET/CT system using the national electrical manufacturers association NU 2-2012 Standard.

The GE Discovery MI PET/CT system has a modular digital detector design allowing three, four, or five detector block rings that extend the axial field-of-view (FOV) from 15 to 25 cm in 5 cm increments. This study investigated the performance of the 5-ring system and compared it to 3- and 4-ring systems; the GE Discovery IQ system that uses conventional photomultiplier tubes; and the GE Signa PET/MR system that has a reduced transaxial FOV. METHODS: PET performance was evaluated at three different institutions. Spatial resolution, sensitivity, counting rate performance, accuracy, and image quality were measured in accordance with National Electrical Manufacturers Association NU 2-2012 standards. The mean energy resolution, mean timing resolution, and PET/CT subsystem alignment were also measured. Phantoms were used to determine the effects of varying acquisition time and reconstruction parameters on image quality. Retrospective patient scans were reconstructed with various scan durations to evaluate the impact on image quality. RESULTS: Results from all three institutions were similar. Radial/tangential/axial full width at half maximum spatial resolution measurements using the filtered back projection algorithm were 4.3/4.3/5.0 mm, 5.5/4.6/6.5 mm, and 7.4/5.0/6.6 mm at 1, 10, and 20 cm from the center of the FOV, respectively. Measured sensitivity at the center of the FOV (20.84 cps/kBq) was significantly higher than systems with reduced axial FOV. The peak noise-equivalent counting rate was 266.3 kcps at 20.8 kBq/ml, with a corresponding scatter fraction of 40.2%. The correction accuracy for count losses up to the peak noise-equivalent counting rate was 3.6%. For the 10-, 13-, 17-, 22-, 28-, and 37-mm spheres, contrast recoveries in the image quality phantom were measured to be 46.2%, 54.3%, 66.1%, 71.1%, 85.3%, and 89.3%, respectively. The mean energy and timing resolution were 9.55% and 381.7 ps, respectively. Phantom and patient images demonstrated excellent image quality, even at short acquisition times or low injected activity. CONCLUSION: Compared to other PET/CT models, the extended axial FOV improved the overall PET performance of the 5-ring GE Discovery MI scanner. This system offers the potential to reduce scan times or injected activities through increased sensitivity.

Oxygen Sensing with Perfluorocarbon-Loaded Ultraporous Mesostructured Silica Nanoparticles.

Oxygen homeostasis is important in the regulation of biological function. Disease progression can be monitored by measuring oxygen levels, thus producing information for the design of therapeutic treatments. Noninvasive measurements of tissue oxygenation require the development of tools with minimal adverse effects and facile detection of features of interest. Fluorine magnetic resonance imaging (19F MRI) exploits the intrinsic properties of perfluorocarbon (PFC) liquids for anatomical imaging, cell tracking, and oxygen sensing. However, the highly hydrophobic and lipophobic properties of perfluorocarbons require the formation of emulsions for biological studies, though stabilizing these emulsions has been challenging. To enhance the stability and biological loading of perfluorocarbons, one option is to incorporate perfluorocarbon liquids into the internal space of biocompatible mesoporous silica nanoparticles. Here, we developed perfluorocarbon-loaded ultraporous mesostructured silica nanoparticles (PERFUMNs) as 19F MRI detectable oxygen-sensing probes. Ultraporous mesostructured silica nanoparticles (UMNs) have large internal cavities (average = 1.8 cm3 g-1), facilitating an average 17% loading efficiency of PFCs, meeting the threshold fluorine concentrations needed for imaging studies. Perfluoro-15-crown-5-ether PERFUMNs have the highest equivalent nuclei per PFC molecule and a spin-lattice (T1) relaxation-based oxygen sensitivity of 0.0032 mmHg-1 s-1 at 16.4 T. The option of loading PFCs after synthesizing UMNs, rather than traditional in situ core-shell syntheses, allows for use of a broad range of PFC liquids from a single material. The biocompatible and tunable chemistry of UMNs combined with the intrinsic properties of PFCs makes PERFUMNs a MRI sensor with potential for anatomical imaging, cell tracking, and metabolic spectroscopy with improved stability.

Development and Validation of Noninvasive Magnetic Resonance Relaxometry for the In Vivo Assessment of Tissue-Engineered Graft Oxygenation.

Techniques to monitor the oxygen partial pressure (pO2) within implanted tissue-engineered grafts (TEGs) are critically necessary for TEG development, but current methods are invasive and inaccurate. In this study, we developed an accurate and noninvasive technique to monitor TEG pO2 utilizing proton (1H) or fluorine (19F) magnetic resonance spectroscopy (MRS) relaxometry. The value of the spin-lattice relaxation rate constant (R1) of some biocompatible compounds is sensitive to dissolved oxygen (and temperature), while insensitive to other external factors. Through this physical mechanism, MRS can measure the pO2 of implanted TEGs. We evaluated six potential MRS pO2 probes and measured their oxygen and temperature sensitivities and their intrinsic R1 values at 16.4 T. Acellular TEGs were constructed by emulsifying porcine plasma with perfluoro-15-crown-5-ether, injecting the emulsion into a macroencapsulation device, and cross-linking the plasma with a thrombin solution. A multiparametric calibration equation containing R1, pO2, and temperature was empirically generated from MRS data and validated with fiber optic (FO) probes in vitro. TEGs were then implanted in a dorsal subcutaneous pocket in a murine model and evaluated with MRS up to 29 days postimplantation. R1 measurements from the TEGs were converted to pO2 values using the established calibration equation and these in vivo pO2 measurements were simultaneously validated with FO probes. Additionally, MRS was used to detect increased pO2 within implanted TEGs that received supplemental oxygen delivery. Finally, based on a comparison of our MRS data with previously reported data, ultra-high-field (16.4 T) is shown to have an advantage for measuring hypoxia with 19F MRS. Results from this study show MRS relaxometry to be a precise, accurate, and noninvasive technique to monitor TEG pO2 in vitro and in vivo.