Ultrasound-induced and MRI-monitored CuO nanoparticles release from micelle encapsulation.

Copper oxide nanoparticles (CuO NPs) have anticancer and antimicrobial activities. Moreover, they have a contrast enhancing effect in both MRI and ultrasound. Nonetheless, encapsulation is needed to control their toxic side effects and a mechanism for release on demand is required. A methodology is introduced herein for encapsulating and releasing CuO NPs from micelles by ultrasound induced hyperthermia and monitoring the process by MRI. For this aim, CuO NPs loaded poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles were prepared. Then, the profile of copper release with application of ultrasound was examined as a function of time and temperature using a colorimetric method. Finally, T1 weighted MRI images of suspensions and ex vivo poultry liver samples containing the CuO NPs loaded micelles were acquired before and after ultrasound application. The results confirmed that: (i) encapsulated NPs are detectible by MRI T1 mapping, depicting substantial T1 shortening from 1872 ± 62 ms to 683 ± 20 ms. (ii) Ultrasonic hyperthermia stimulated the NPs release with an about threefold increase compared to non-treated samples. (iii) Releasing effect was clearly visible by T1-weighted imaging (mean signal increase ratio of 2.29). These findings can potentially lead to the development of a new noninvasive methodology for CuO NPs based theranostic process.

Laser-induced thermal response and controlled release of copper oxide nanoparticles from multifunctional polymeric nanocarriers.

Multifunctional nanocarriers have attracted considerable interest in improving cancer treatment outcomes. Poly(lactide-co-glycolide) (PLGA) nanospheres encapsulating copper oxide nanoparticles (CuO-NPs) are characterized by antitumor activity and exhibit dual-modal contrast-enhancing capabilities. An in vitro evaluation demonstrates that this delivery system allows controlled and sustained release of CuO-NPs. To achieve localized release on demand, an external stimulation by laser irradiation is suggested. Furthermore, to enable simultaneous complementary photothermal therapy, polydopamine (PDA) coating for augmented laser absorption is proposed. To this aim, two formulations of CuO-NPs loaded nanospheres are prepared from PLGA polymers RG-504 H (H-PLGA) and RG-502 H (L-PLGA) as scaffolds for surface modification through in situ polymerization of dopamine and then PEGylation. The obtained CuO-NPs-based multifunctional nanocarriers are characterized, and photothermal effects are examined as a function of wavelength and time. The results show that 808 nm laser irradiation of the coated nanospheres yields maximal temperature elevation (T = 41°C) and stimulates copper release at a much faster rate compared to non-irradiated formulations. Laser-triggered CuO-NP release is mainly depended on the PLGA core, resulting in faster release with L-PLGA, which also yielded potent anti-tumor efficacy in head and neck cancer cell line (Cal-33). In conclusion, the suggested multifunctional nanoplatform offers the integrated benefits of diagnostic imaging and laser-induced drug release combined with thermal therapy.

Speed of Sound and Attenuation Temperature Dependence of Bovine Brain: Ex Vivo Study.

OBJECTIVES: Brain treatments using focused ultrasound (FUS) offer a new range of noninvasive transcranial therapies. The acoustic energy deposition during these procedures may induce a temperature elevation in the tissue; therefore, noninvasive thermal monitoring is essential. Magnetic resonance imaging is the current adopted monitoring modality, but its high operational costs and limited availability may hinder the accessibility to FUS treatments. Aiming at the development of a thermometric ultrasound (US) method for the brain, the specific objective of this investigation was to study the acoustic thermal response of the speed of sound (SOS) and attenuation coefficient (AC) of different brain tissues: namely white matter (WM) and cortical matter. METHODS: Sixteen ex vivo bovine brain samples were investigated. These included 7 WM and 9 cortical matter samples. The samples were gradually heated to about 45°C and then repeatedly scanned while cooling using a computerized US system in the through-transmission mode. The temperature was simultaneously registered with thermocouples. From the scans, the normalized SOS and AC for both tissues were calculated. RESULTS: The results demonstrated a characteristic cooldown temporal behavior for the normalized AC and SOS curves, which were related to the temperature. The SOS curves enabled clear differentiation between the tissue types but depicted more scattered trajectories for the WM tissue. As for the AC curves, the WM depicted a linear behavior in relation to the temperature. However, both tissue types had rather similar temperature patterns. CONCLUSIONS: These findings may contribute to the development of a US temperature-monitoring method during FUS procedures.

Copper oxide loaded PLGA nanospheres: towards a multifunctional nanoscale platform for ultrasound-based imaging and therapy.

Copper oxide nanoparticles (CuO-NPs) are increasingly becoming the subject of investigation exploring their potential use for diagnostic and therapeutic purposes. Recent work has demonstrated their anticancer potential, as well as contrast agent capabilities for magnetic resonance imaging (MRI) and through-transmission ultrasound. However, no capability of CuO-NPs has been demonstrated using conventional ultrasound systems, which, unlike the former, are widely deployed in the clinic. Furthermore, in spite of their potential as multifunctional nano-based materials for diagnosis and therapy, CuO-NPs have been delayed from further clinical application due to their inherent toxicity. Herein, we present the synthesis of a novel nanoscale system, composed of CuO-loaded PLGA nanospheres (CuO-PLGA-NS), and demonstrate its imaging detectability and augmented heating effect by therapeutic ultrasound. The CuO-PLGA-NS were prepared by a double emulsion (W/O/W) method with subsequent solvent evaporation. They were characterized as sphere-shaped, with size approximately 200 nm. Preliminary results showed that the viability of PANC-1, human pancreatic adenocarcinoma cells was not affected after 72 h exposure to CuO-PLGA-NS, implying that PLGA masks the toxic effects of CuO-NPs. A systematic ultrasound imaging evaluation of CuO-PLGA-NS, using a conventional system, was performed in vitro and ex vivo using poultry heart and liver, and also in vivo using mice, all yielding a significant contrast enhancement. In contrast to CuO-PLGA-NS, neither bare CuO-NPs nor blank PLGA-NS possess these unique advantageous ultrasonic properties. Furthermore, CuO-PLGA-NS accelerated ultrasound-induced temperature elevation by more than 4 °C within 2 min. The heating efficiency (cumulative equivalent minutes at 43 °C) was increased approximately six-fold, demonstrating the potential for improved ultrasound ablation. In conclusion, CuO-PLGA-NS constitute a versatile platform, potentially useful for combined imaging and therapeutic ultrasound-based procedures.

Target visualisation and microwave hyperthermia monitoring using nanoparticle-enhanced transmission ultrasound (NETUS).

PURPOSE: The aim of this study was to examine the feasibility of using nanoparticle-enhanced transmission ultrasound (NETUS) as an image-based monitoring modality for microwave hyperthermia treatment. METHODS: A dedicated transmission ultrasound imaging system was used to obtain acoustic projections and ultrasound computed tomography images. Initially, speed-of-sound based images were used to non-invasively monitor temperature changes in in vitro and ex vivo specimens, induced by a microwave needle-type applicator. Next, the hyperthermia acceleration ability of two ultrasound nanoparticles based contrast agents (iron oxide and copper oxide) was examined and visualised. Finally, a two-step image guided microwave therapeutic procedure using NETUS was investigated in a realistic breast mimicking phantom. First, the pathology simulating region borders were detected. Then, a microwave-induced temperature elevation was non-invasively monitored. RESULTS: The transmission ultrasound scanning system was able to detect temperature changes with a resolution of less than 0.5 °C, both in vitro and ex vivo. In accordance with previous studies, it was visually demonstrated that iron oxide nanoparticles expedite the heating process (p < 0.05). Copper oxide nanoparticles, however, did not alter the hyperthermia profile significantly. In the breast mimicking phantom, NETUS yielded accurate detection of the target region as well as thermal monitoring of the microwave heating procedure. CONCLUSIONS: NETUS can combine enhanced target visualisation with non-invasive thermometry and accelerated heating effect. Quantitative feedback, however, requires a tissue-specific calibration-curve. A proof of concept for microwave hyperthermia treatment monitoring using NETUS was established. The suggested methodology may potentially provide a non-invasive cost-effective means for monitoring thermal treatment of the breast.

Optical flow and image segmentation analysis for noninvasive precise mapping of microwave thermal ablation in X-ray CT scans - ex vivo study.

PURPOSE: To develop image processing algorithms for noninvasive mapping of microwave thermal ablation using X-ray CT. METHODS: Ten specimens of bovine liver were subjected to microwave ablation (20-80 W, 8 min) while scanned by X-ray CT at 5 s intervals. Specimens were cut and manually traced by two observers. Two algorithms were developed and implemented to map the ablation zone. The first algorithm utilises images segmentation of Hounsfield units changes (ISHU). The second algorithm utilises radial optical flow (ROF). Algorithm sensitivity to spatiotemporal under-sampling was assessed by decreasing the acquisition rate and reducing the number of acquired projections used for image reconstruction in order to evaluate the feasibility of implementing radiation reduction techniques. RESULTS: The average radial discrepancy between the ISHU and ROF contours and the manual tracing were 1.04±0.74 and 1.16±0.79mm, respectively. When diluting the input data, the ISHU algorithm retained its accuracy, ranging from 1.04 to 1.79mm. By contrast, the ROF algorithm performance became inconsistent at low acquisition rates. Both algorithms were not sensitive to projections reduction, (ISHU: 1.24±0.83mm, ROF: 1.53±1.15mm, for reduction by eight fold). Ablations near large blood vessels affected the ROF algorithm performance (1.83±1.30mm; p < 0.01), whereas ISHU performance remained the same. CONCLUSION: The two suggested noninvasive ablation mapping algorithms can provide highly accurate contouring of the ablation zone at low scan rates. The ISHU algorithm may be more suitable for clinical practice as it appears more robust when radiation dose reduction strategies are employed and when the ablation zone is near large blood vessels.

Non-invasive temperature monitoring and hyperthermic injury onset detection using X-ray CT during HIFU thermal treatment in ex vivo fatty tissue.

PURPOSE: This paper examines X-ray CT, to serve as an image-guiding thermal monitoring modality for high intensity focused ultrasound (HIFU) treatment of fatty tissues. MATERIALS AND METHODS: Six ex vivo porcine fat tissue specimens were scanned by X-ray CT simultaneously with the application of HIFU. Images were acquired during both heating and post-ablation stages. The temperature at the focal zone was measured simultaneously using a thermocouple. The mean values of the Hounsfield units (HU) at the focal zone were registered and plotted as a function of temperature. RESULTS: In all specimens studied, the HU versus temperature curves measured during the heating stage depicted a characteristic non-linear parabolic trajectory (R(2) > 0.87). The HU-temperature trajectory initially decreased to a minimum value at about 44.5 °C and then increased substantially as the heating progressed. The occurrence of this nadir point during the heating stage was clearly detectable. During post-ablation cooling, on the other hand, the HU increased monotonically with the decreasing temperature and depicted a clearly linear trajectory (R(2) ≥ 0.9). CONCLUSIONS: Our results demonstrate that the HU-temperature curve during HIFU treatment has a characteristic parabolic trajectory for fat tissue that might potentially be utilised for thermal monitoring during HIFU ablation treatments. The clear detection of 44.5 °C, presumably marking the onset of hyperthermic injury, can be detected non-invasively as an occurrence of a minimum on the HU-time curve without any need to relate the HU directly to temperature. Such features may be helpful in monitoring and optimising HIFU thermal treatment for clinically applicable indications such as in the breast by providing a non-invasive monitoring of tissue damage.

Temperature-density hysteresis in X-ray CT during HIFU thermal ablation: heating and cooling phantom study.

PURPOSE: This paper investigated the effects of thermal ablation treatment on imaged X-ray computed tomography (CT) Hounsfield units (HU), for the purpose of monitoring tissue denaturation and coagulation. MATERIALS AND METHODS: Eight phantoms of water, oil, and chicken serum albumin as well as 15 ex vivo tissue samples were heated by applying high intensity focused ultrasound (HIFU) for 10 to 29 min to obtain denaturation temperatures, (i.e. >50 °C). X-ray CT scanning was performed simultaneously during heating and post-ablation cooling stages, and the HU at the focal zone were registered. The temperature profile versus time was also monitored under similar conditions using a thermocouple probe. The results were plotted and correlated as curves of HU versus temperature. RESULTS: In all specimens studied, HU values depicted an exponential curve as a function of temperature during the heating stage. However, linear behaviour was observed during the cool-down stage for both chicken serum albumin and ex vivo bovine liver. Thus, a hysteresis phenomenon occurred only when the thermal conditions induced irreversible changes in the sample with quantification demonstrating high correlation with the maximal temperature reached during treatment (R(2)> 0.9) for the chicken serum albumin. CONCLUSIONS: Our results demonstrate a HU-temperature hysteresis phenomenon for HIFU ablation, which is detectible by X-ray CT. This hysteresis is related to the amount of heat induced into the tissue and could potentially indicate irreversible tissue damage. Accordingly, this measurable phenomenon can be utilised as a quantitative method for non-invasive monitoring of thermal ablation.

Ultrasound Mediated Polymerization for Cell Delivery, Drug Delivery, and 3D Printing.

Safe and accurate in situ delivery of biocompatible materials is a fundamental requirement for many biomedical applications. These include sustained and local drug release, implantation of acellular biocompatible scaffolds, and transplantation of cells and engineered tissues for functional restoration of damaged tissues and organs. The common practice today includes highly invasive operations with major risks of surgical complications including adjacent tissue damage, infections, and long healing periods. In this work, a novel non-invasive delivery method is presented for scaffold, cells, and drug delivery deep into the body to target inner tissues. This technology is based on acousto-sensitive materials which are polymerized by ultrasound induction through an external transducer in a rapid and local fashion without additional photoinitiators or precursors. The applicability of this technology is demonstrated for viable and functional cell delivery, for drug delivery with sustained release profiles, and for 3D printing. Moreover, the mechanical properties of the delivered scaffold can be tuned to the desired target tissue as well as controlling the drug release profile. This promising technology may shift the paradigm for local and non-invasive material delivery approach in many clinical applications as well as a new printing method - "acousto-printing" for 3D printing and in situ bioprinting.

Safety and tolerability of a focused ultrasound device for treatment of adipose tissue in subjects undergoing abdominoplasty: a placebo-control pilot study.

BACKGROUND: High-intensity focused ultrasound (HIFU) lipolysis is a noninvasive alternative to existing surgical body-sculpting methods. OBJECTIVE: To evaluate the safety, tolerability, and histologic outcome of HIFU lipolysis using a novel device in human subjects. METHODS AND MATERIALS: In a single-blind pilot study, six healthy subjects scheduled to undergo abdominoplasty within 4 weeks received HIFU lipolysis on one side of the umbilicus. An identical placebo treatment was given to the contralateral side. Patient evaluation of complications, blood tests, and urine analysis were performed 1, 3, 7, 14, and 28 days after treatment. Excised tissue from the treated areas was sent for histologic review. RESULTS: Treatment was well tolerated. Average visual analogue pain scale scores were 3.5 ± 2.3 (range 1-7) and 0.17 ± 0.41 (range 0-1). No major adverse events were documented, and laboratory analysis after HIFU lipolysis was normal. Fat necrosis with infiltration of lymphocytes and macrophages without adjacent tissue damage was documented on histology 2 to 4 weeks after HIFU lipolysis. Damage extent correlated with size of the area treated. No pathologic findings were found on the control side. CONCLUSIONS: High-intensity focused ultrasound treatment was well tolerated and safe. Focal damage to target tissue was documented, with adjacent tissues remaining intact.

Noninvasive lipoma size reduction using high-intensity focused ultrasound.

BACKGROUND: Lipomas are common benign mesenchymal tumors commonly removed using excision, but in certain cases, surgery is undesirable or ineffective. High-intensity focused ultrasound (HIFU) offers a noninvasive tumor ablation tool increasingly used in the clinic. OBJECTIVE: To evaluate the efficacy and safety of a noninvasive lipoma size reduction technology using HIFU. MATERIALS & METHODS: Twelve lipomas in nine patients were treated. Patients underwent four treatment sessions with a 3-week interval between treatments. Blood and urine tests and tolerability based on a standard visual analogue scale (VAS) were used to monitor patients for adverse effects. Lipoma volume was determined by measuring width and length (manually) and depth (ultrasonically). RESULTS: The range of lipoma size was 2.7-169.4 cm3 before treatment and 0.2-119.8 cm3 after treatment. Mean volume reduction was 58.1 ± 22.8%. When palpated, the lipomas felt much softer than before treatment. The average VAS score was 4.1 ± 2.4. No significant adverse effects were noted. CONCLUSION: The treatment was shown to be effective in noninvasively reducing lipoma size. The average volume reduction was substantial and statistically significant. The treatment was safe and well-tolerated. HIFU may be an alternative treatment modality in cases of lipoma.

Feasibility study of contrast-enhanced automated acoustic mammography.

The feasibility of implementing image subtraction in through-transmission breast sonography was examined. Acoustic mammograms of women with suspicious findings were obtained using through-transmission imaging. Precontrast images were initially acquired. Then a perflutren liquid microsphere contrast agent solution was injected intravenously, and new sets of images were acquired. Precontrast-postcontrast subtraction images depicting the resulting changes were then obtained and visually compared with other imaging modalities. The ability to detect changes stemming from contrast agent injection in the through-transmission mode was verified. The comparability with x-ray mammography and magnetic resonance imaging was shown. Finally, the ability to compare images obtained before and several months after surgery was confirmed.

Image Translation of Breast Ultrasound to Pseudo Anatomical Display by CycleGAN.

Ultrasound imaging is cost effective, radiation-free, portable, and implemented routinely in clinical procedures. Nonetheless, image quality is characterized by a granulated appearance, a poor SNR, and speckle noise. Specific for breast tumors, the margins are commonly blurred and indistinct. Thus, there is a need for improving ultrasound image quality. We hypothesize that this can be achieved by translation into a more realistic display which mimics a pseudo anatomical cut through the tissue, using a cycle generative adversarial network (CycleGAN). In order to train CycleGAN for this translation, two datasets were used, "Breast Ultrasound Images" (BUSI) and a set of optical images of poultry breast tissues. The generated pseudo anatomical images provide improved visual discrimination of the lesions through clearer border definition and pronounced contrast. In order to evaluate the preservation of the anatomical features, the lesions in both datasets were segmented and compared. This comparison yielded median dice scores of 0.91 and 0.70; median center errors of 0.58% and 3.27%; and median area errors of 0.40% and 4.34% for the benign and malignancies, respectively. In conclusion, generated pseudo anatomical images provide a more intuitive display, enhance tissue anatomy, and preserve tumor geometry; and can potentially improve diagnoses and clinical outcomes.

Ultrasonic Thermal Monitoring of the Brain Using Golay-Coded Excitations-Feasibility Study.

Thermal monitoring during focused ultrasound (FUS) transcranial procedures is mandatory and commonly performed by MRI. Transcranial ultrasonic thermal monitoring is an attractive alternative. Furthermore, using the therapeutic FUS transducer itself for this task is highly desirable. Nonetheless, such application is challenged by massive skull-induced signal attenuation and aberrations. This study examined the feasibility of implementing the Golay-coded excitations (CoE) for temperature monitoring in bovine brain samples in the range of 35 °C-43 °C (hyperthermia). Feasibility was assessed using computer simulations, water-based phantoms, and ex vivo bovine brain white-matter samples. The samples were gradually heated to about 45 °C and sonicated during cool down with a 1-MHz therapeutic FUS implementing Golay CoE. Initially, a calibration curve correlating the normalized time-of-flight (TOF) changes and the temperature was generated. Next, a bovine bone was positioned between the FUS and the brain samples, and the scanning process was repeated for different fresh samples. The calibration curve was then used as a mean for estimating the temperature, which was compared to thermocouple measurements. The simulations demonstrated a substantial improvement in signal-to-noise ratio (SNR) and suggested that the implementation of 4-bit sequences is advantageous. The experimental measurements with bone demonstrated good temperature estimation with an average absolute error for the water phantoms and brains of 1.46 °C ± 1.22 °C and 1.23 °C ± 0.99 °C, respectively. In conclusion, a novel noninvasive method utilizing the Golay CoE for ultrasonic thermal monitoring using a therapeutic FUS transducer is introduced. This method can lead to the development of an acoustic tool for brain thermal monitoring.

A method for characterization of tissue elastic properties combining ultrasonic computed tomography with elastography.

OBJECTIVE: The correlation between various diseases and the change in the local mechanical properties of soft tissues has been long known. Over the past 20 years, there have been increasing research efforts to characterize mechanical properties of biological tissues using ultrasonic elastography. However, most of these works were based on characterization of only 1 type of waves (longitudinal or shear). The goal of this work was to devise a comprehensive ultrasound-based imaging method capable of measuring elastic parameters by combining both backscattered elastography and through-transmitted ultrasonic computed tomography. METHODS: Our suggested technique provides measurements of both longitudinal and shear wave velocities. This enables the noninvasive computation of several tissue elasticity parameters such as Young's and shear moduli, Poisson's ratio, and, more importantly, the bulk modulus, the determination of which requires both wave velocities. Four different phantom types were examined: agar-gelatin-based phantoms and porcine fat tissue, turkey breast tissue, and bovine liver tissue in vitro specimens. The values of Young's modulus, the shear modulus, and Poisson's ratio were estimated and were consistent with values published in the literature. RESULTS: The average bulk modulus values of the phantoms +/- SD were 2.83 +/- 0.001, 2.25 +/- 0.01, 2.48 +/- 0.01, and 2.53 +/- 0.02 GPa, respectively. A statistically significant difference (P < .001) in the values of the bulk modulus of the different phantoms was found. CONCLUSIONS: The bulk modulus is suitable for differentiation between different tissue types. The obtained results show the feasibility of using a comprehensive ultrasonic imaging technique for noninvasive quantitative tissue characterization.

In vivo noninvasive three-dimensional (3D) assessment of microwave thermal ablation zone using non-contrast-enhanced x-ray CT.

PURPOSE: To develop an image processing methodology for noninvasive three-dimensional (3D) quantification of microwave thermal ablation zones in vivo using x-ray computed tomography (CT) imaging without injection of a contrast enhancing material. METHODS: Six microwave (MW) thermal ablation procedures were performed in three pigs. The ablations were performed with a constant heating duration of 8 min and power level of 30 W. During the procedure images from sixty 1 mm thick slices were acquired every 30 s. At the end of all ablation procedures for each pig, a contrast-enhanced scan was acquired for reference. Special algorithms for addressing challenges stemming from the 3D in vivo setup and processing the acquired images were prepared. The algorithms first rearranged the data to account for the oblique needle orientation and for breathing motion. Then, the gray level variance changes were analyzed, and optical flow analysis was applied to the treated volume in order to obtain the ablation contours and reconstruct the ablation zone in 3D. The analysis also included a special correction algorithm for eliminating artifacts caused by proximal major blood vessels and blood flow. Finally, 3D reference reconstructions from the contrast-enhanced scan were obtained for quantitative comparison. RESULTS: For four ablations located >3 mm from a large blood vessel, the mean dice similarity coefficient (DSC) and the mean absolute radial discrepancy between the contours obtained from the reference contrast-enhanced images and the contours produced by the algorithm were 0.82 ± 0.03 and 1.92 ± 1.47 mm, respectively. In two cases of ablation adjacent to large blood vessels, the average DSC and discrepancy were: 0.67 ± 0.6 and 2.96 ± 2.15 mm, respectively. The addition of the special correction algorithm utilizing blood vessels mapping improved the mean DSC and the mean absolute discrepancy to 0.85 ± 0.02 and 1.19 ± 1.00 mm, respectively. CONCLUSIONS: The developed algorithms provide highly accurate detailed contours in vivo (average error < 2.5 mm) and cope well with the challenges listed above. Clinical implementation of the developed methodology could potentially provide real time noninvasive 3D accurate monitoring of MW thermal ablation in-vivo, provided that the radiation dose can be reduced.

Correction for respiration artefacts in myocardial perfusion SPECT is more effective when reconstructions supporting collimator detector response compensation are applied.

PURPOSE: To assess the impact of respiration on myocardial perfusion imaging (MPI) SPECT processed with advanced algorithmic reconstructions. METHODS: SPECT studies obtained from a phantom simulation and 49 respiratory-gated,one-day 99mTc-sestamibi scans were corrected for respiratory-related cardiac movement. Three types of reconstruction algorithms: (a) filtered back projection (FBP), (b) ordered subset expectation maximization in which collimator detector response was incorporated (OSEMCDR), and (c) OSEM-CDR with additional attenuation and scatter corrections (OSEM-CDRACSC) were applied to the corrected and uncorrected sets and analyzed quantitatively and qualitatively. RESULTS: A discrepancy between the corrected and uncorrected bull's eye maps > or = 10% wasfound in 2%, 10%, and 20% of the FBP, OSEM-CDR, and OSEM-CDR-ACSC scans, respectively. In studies with more than 10-mm respiratory motion, the effect of motion was greater in OSEM-CDR and OSEM-CDR-ACSC datasets as compared to FBP processing.Qualitative and quantitative differences between corrected and uncorrected sets were significantly larger in OSEM-CDR and OSEM-CDR-ACSC data than in those of FBP data. CONCLUSIONS: Respiratory-related cardiac motion significantly affects MPI-SPECT reconstructed with advanced high-resolution reconstruction algorithms such as OSEM-CDR and OSEM-CDR-ACSC and thus may justifies the application of respiratory gating.

Dual "motion-frozen heart" combining respiration and contraction compensation in clinical myocardial perfusion SPECT imaging.

OBJECTIVES: This article assesses the effect of a new correction technique ("motion-frozen heart") which compensates for the previously described nonuniform blurring of myocardial perfusion imaging (MPI) due to respiration motion or cardiac contraction. METHODS: Respiratory and ECG-gated one-day (99m)Tc-MIBI MPI studies performed in 48 patients were evaluated. MPI scans were acquired on a gamma camera supporting list-mode functionality synchronized with an external respiratory strap and an ECG device. Respiratory and cardiac-gated bins were generated using the acquired list file. Respiratory-gated bins were corrected for respiratory motion, followed by correction for cardiac contraction motion. In addition, cardiac contraction correction was applied to cardiac-gated bins uncorrected for respiratory motion. Bullseye maps were generated for uncorrected MPI studies, as well as following correction for respiratory motion, cardiac contraction, and both. The mean difference between each of the correction vs the uncorrected bullseye was calculated. Visual assessment of image quality, severity, and extent of the uncorrected perfusion images and following each of the corrections was performed. RESULTS: Average motion due respiration was 7.0 +/- 2.6 mm in the axial plane. The maximal score difference in segmental uptake greater than 10% was found in 2%, 15%, and 25% following respiratory correction, contraction correction, and dual corrections, respectively. Percent of scans classified with an excellent image quality was 13%, 21%, 42%, and 52% for the uncorrected images and following respiratory correction, contraction correction, and dual corrections, respectively. CONCLUSIONS: A technique that compensates for motion of the heart due to respiration and cardiac contraction in MPI-SPECT was evaluated. Compensating for both respiration and cardiac contraction had the greatest effect on perfusion images resulting in significantly improved image quality.

CORE-PI: Non-iterative convolution-based reconstruction for parallel MRI in the wavelet domain.

PURPOSE: To develop and test a novel parameter-free non-iterative wavelet domain method for reconstruction of undersampled multicoil MR data. THEORY AND METHODS: A linear parallel MRI method that operates in the Stationary Wavelet Transform (SWT) domain is proposed. The method is coined COnvolution-based REconstruction for Parallel MRI (CORE-PI). This method computes the SWT of the unknown MR image directly from subsampled k-space measurements, without modifying the RF excitation pulse. It then reconstructs the image using the wavelet filter bank approach, with simple linear computations. The CORE-PI implementation is demonstrated by experiments with a numeric brain phantom and in vivo brain scans data, with various wavelet types and high reduction factors. It is compared to the well-known parallel MRI methods GRAPPA and l1-SPIRiT. RESULTS: The experimental results show that CORE-PI is suitable for different 1D Cartesian k-space undersampling schemes, including regular and irregular ones, and for wavelets of different families. CORE-PI accurately reconstructs the SWT coefficients of the unknown MR image; this wavelet-domain decomposition is fully computed despite the k-space undersampling. Furthermore, CORE-PI provides high-quality final reconstructions, with an average NRMSE of 0.013, which is significantly lower than that obtained by GRAPPA and l1-SPIRiT. Moreover, CORE-PI offers significantly faster computation times: the typical CORE-PI runtime is about 60 seconds, which is about 20% shorter than that of l1-SPIRiT and 55%-75% shorter than that of GRAPPA. CONCLUSION: COnvolution-based REconstruction for Parallel MRI advantageously offers: (a) flexible 1D undersampling of a Cartesian k-space, (b) a parameter-free non-iterative implementation, (c) reconstruction performance comparable or better than that of GRAPPA and l1-SPIRiT, and (d) robust fast computations.

Copper oxide nanoparticles inhibit pancreatic tumor growth primarily by targeting tumor initiating cells.

Cancer stem cells, also termed tumor initiating cells (TICs), are a rare population of cells within the tumor mass which initiate tumor growth and metastasis. In pancreatic cancer, TICs significantly contribute to tumor re-growth after therapy, due to their intrinsic resistance. Here we demonstrate that copper oxide nanoparticles (CuO-NPs) are cytotoxic against TIC-enriched PANC1 human pancreatic cancer cell cultures. Specifically, treatment with CuO-NPs decreases cell viability and increases apoptosis in TIC-enriched PANC1 cultures to a greater extent than in standard PANC1 cultures. These effects are associated with increased reactive oxygen species (ROS) levels, and reduced mitochondrial membrane potential. Furthermore, we demonstrate that CuO-NPs inhibit tumor growth in a pancreatic tumor model in mice. Tumors from mice treated with CuO-NPs contain a significantly higher number of apoptotic TICs in comparison to tumors from untreated mice, confirming that CuO-NPs target TICs in vivo. Overall, our findings highlight the potential of using CuO-NPs as a new therapeutic modality for pancreatic cancer.