Imaging Time Window Research Articles

Use of Second Window ICG in spinal cord biopsy of a mildly contrast-enhancing lesion: Technical note and review of the literature

IntroductionIndocyanine green (ICG) is commonly used to visualize cerebral vasculature, particularly in the management of cerebral aneurysms. There have also been attempts to use ICG for visualization of tumors. Injection of ICG followed by immediate fluorescence microscopy is limited by the short time window for imaging and administration and restricted depth of imaging. Second Window Indocyanine Green (SWIG) addresses these issues by allowing for longer contrast times and the imaging of deeper regions of brain tissue. Biopsy of spinal cord lesions is often difficult for a variety of reasons, including the delicate nature of the tissue and differentiating normal from lesional tissue visually, especially in lesions with heterogeneous enhancement. MethodsIn this case report, we describe the use of second window ICG to facilitate the visualization of a spinal cord lesion and subsequent biopsy of the lesion. ResultsThis patient is a 24-year-old female who had recurrence of a suprasellar germinoma. An MRI of the rest of the neuraxis was performed to assess for the presence of drop metastases. The spinal cord from C2-5 was expanded with areas of patchy enhancement; however, this lesion was asymptomatic. The patient's oncologist requested a biopsy of this lesion to help direct subsequent care of her recurrent germinoma. The day before surgery, the patient had an intravenous injection of ICG dye. She then underwent a C3-5 laminectomy for biopsy of her cervical intramedullary lesion. After opening of the dura, no visible abnormality of the spinal cord could be identified. A Stryker endoscope showed an area of ICG uptake in the cord at approximately the C3-4 level. A midline myelotomy was centered over the ICG demarcated area and several samples were taken for pathology. Final biopsy results determined the lesion to be spinal cord parenchyma with perivascular and intraparenchymal lymphocytes – not consistent with spinal cord tumor or germinoma. ConclusionSecond Window ICG is effective in visualizing otherwise visually unremarkable spinal cord lesions. This technology can facilitate biopsy of these lesions and possibly their surgical resection.

A Mission Planning Modeling Method of Multipoint Target Imaging Within a Single Pass for Super-Agile Earth Observation Satellite

The existing mission planning models for conventional agile Earth observation satellites assuming stable push-broom imaging cannot be directly adapted to newly developed superagile Earth observation satellites (SA-EOS) with dynamic imaging capabilities. To guarantee the application efficiency of SA-EOS, a novel mission planning modeling method for multipoint target imaging within a single pass (MTI-SP) is proposed. First, a two-step preprocessing method for point targets based on the “nonalong-track” characteristic of SA-EOS converts multiple point targets into imaging strips as an atomic mission for further planning. Then, a triple of decision variables is defined, i.e., the index of the imaging sequence of multiple strips, indices of the push-broom direction of the strips, and normalization coefficients of the imaging time of each endpoint of the strips, on the basis of the one-to-one correspondence between the triple and the imaging time. Third, an optimal MTI-SP mission planning model with two objective functions, namely maximizing the mission coverage benefit (MCB) and minimizing the mission completion time (MCT), is established by considering the imaging time window and attitude transition time. An improved particle swarm optimization algorithm is used for the MTI-SP solution. The results of comparison experiments indicate that the proposed model can achieve the maximum MCB with lower computational consumption. Compared with the two fixed push-broom sequence models and the independent point targets model, the MCT of the proposed model is improved by 47.1%, 24.56%, and 89.45%, respectively. The experiment results show that the proposed modeling method can be further applied in ground operational systems of SA-EOS.

Modeling of Diurnal Changing Patterns in Airborne Crop Remote Sensing Images

Airborne remote sensing technologies have been widely applied in field crop phenotyping. However, the quality of current remote sensing data suffers from significant diurnal variances. The severity of the diurnal issue has been reported in various plant phenotyping studies over the last four decades, but there are limited studies on the modeling of the diurnal changing patterns that allow people to precisely predict the level of diurnal impacts. In order to comprehensively investigate the diurnal variability, it is necessary to collect time series field images with very high sampling frequencies, which has been difficult. In 2019, Purdue agricultural (Ag) engineers deployed their first field visible to near infrared (VNIR) hyperspectral gantry platform, which is capable of repetitively imaging the same field plots every 2.5 min. A total of 8631 hyperspectral images of the same field were collected for two genotypes of corn plants from the vegetative stage V4 to the reproductive stage R1 in the 2019 growing season. The analysis of these images showed that although the diurnal variability is very significant for almost all the image-derived phenotyping features, the diurnal changes follow stable patterns. This makes it possible to predict the imaging drifts by modeling the changing patterns. This paper reports detailed diurnal changing patterns for several selected plant phenotyping features such as Normalized Difference Vegetation Index (NDVI), Relative Water Content (RWC), and single spectrum bands. For example, NDVI showed a repeatable V-shaped diurnal pattern, which linearly drops by 0.012 per hour before the highest sun angle and increases thereafter by 0.010 per hour. The different diurnal changing patterns in different nitrogen stress treatments, genotypes and leaf stages were also compared and discussed. With the modeling results of this work, Ag remote sensing users will be able to more precisely estimate the deviation/change of crop feature predictions caused by the specific imaging time of the day. This will help people to more confidently decide on the acceptable imaging time window during a day. It can also be used to calibrate/compensate the remote sensing result against the time effect.

The Renal Clearable Magnetic Resonance Imaging Contrast Agents: State of the Art and Recent Advances.

The advancements of magnetic resonance imaging contrast agents (MRCAs) are continuously driven by the critical needs for early detection and diagnosis of diseases, especially for cancer, because MRCAs improve diagnostic accuracy significantly. Although hydrophilic gadolinium (III) (Gd3+) complex-based MRCAs have achieved great success in clinical practice, the Gd3+-complexes have several inherent drawbacks including Gd3+ leakage and short blood circulation time, resulting in the potential long-term toxicity and narrow imaging time window, respectively. Nanotechnology offers the possibility for the development of nontoxic MRCAs with an enhanced sensitivity and advanced functionalities, such as magnetic resonance imaging (MRI)-guided synergistic therapy. Herein, we provide an overview of recent successes in the development of renal clearable MRCAs, especially nanodots (NDs, also known as ultrasmall nanoparticles (NPs)) by unique advantages such as high relaxivity, long blood circulation time, good biosafety, and multiple functionalities. It is hoped that this review can provide relatively comprehensive information on the construction of novel MRCAs with promising clinical translation.

Automated synthesis and preliminary evaluation of [18F]FDPA for cardiac inflammation imaging in rats after myocardial infarction

A translocator protein 18 kDa targeted radiotracer, N,N-diethyl-2-(2-(4-[18F]fluorophenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl) acetamide ([18F]FDPA), was automated synthetized and evaluated for cardiac inflammation imaging. Various reaction conditions for an automated synthesis were systematically optimized. MicroPET/CT imaging were performed on normal rats and rats with myocardial infarction (MI). Normalized SUV ratios of [18F]FDPA to [13N]NH3 (NSRs) in different regions were calculated to normalize the uptake of [18F]FDPA to perfusion. The amount of TBAOMs and the volume/proportion of water were crucial for synthesis. After optimization, the total synthesis time was 68 min. The non-decay corrected radiochemical yields (RCYs) and molar activities were 19.9 ± 1.7% and 169.7 ± 46.5 GBq/μmol, respectively. In normal rats, [18F]FDPA showed a high and stable cardiac uptake and fast clearance from other organs. In MI rats, NSRs in the peri-infarct and infarct regions, which were infiltrated with massive inflammatory cells revealed by pathology, were higher than that in the remote region (1.20 ± 0.01 and 1.08 ± 0.10 vs. 0.89 ± 0.05, respectively). [18F]FDPA was automated synthesized with high RCYs and molar activities. It showed a high uptake in inflammation regions and offered a wide time window for cardiac imaging, indicating it could be a potential cardiac inflammation imaging agent.

Anti-GD2-IRDye800CW as a targeted probe for fluorescence-guided surgery in neuroblastoma

Neuroblastoma resection represents a major challenge in pediatric surgery, because of the high risk of complications. Fluorescence-guided surgery (FGS) could lower this risk by facilitating discrimination of tumor from normal tissue and is gaining momentum in adult oncology. Here, we provide the first molecular-targeted fluorescent agent for FGS in pediatric oncology, by developing and preclinically evaluating a GD2-specific tracer consisting of the immunotherapeutic antibody dinutuximab-beta, recently approved for neuroblastoma treatment, conjugated to near-infrared (NIR) fluorescent dye IRDye800CW. We demonstrated specific binding of anti-GD2-IRDye800CW to human neuroblastoma cells in vitro and in vivo using xenograft mouse models. Furthermore, we defined an optimal dose of 1 nmol, an imaging time window of 4 days after administration and show that neoadjuvant treatment with anti-GD2 immunotherapy does not interfere with fluorescence imaging. Importantly, as we observed universal, yet heterogeneous expression of GD2 on neuroblastoma tissue of a wide range of patients, we implemented a xenograft model of patient-derived neuroblastoma organoids with differential GD2 expression and show that even low GD2 expressing tumors still provide an adequate real-time fluorescence signal. Hence, the imaging advancement presented in this study offers an opportunity for improving surgery and potentially survival of a broad group of children with neuroblastoma.

A SATELLITE IMAGING MISSION PLANNING METHOD FOR FAST ANTARCTICA COVERAGE

Abstract. Global warming has become one of the most prominent global issues, and Antarctic ice sheet is one of the indicator of global climate change. Satellite imagery has become an important means of monitoring the changes in Antarctic ice sheet. Due to the high overlap of satellite imaging swaths, the existing Antarctica images have the disadvantages of long period of imagery acquisition, large temporal difference among the mosaic images, and low utilization of satellite resource. This paper proposes a satellite imaging mission planning method for fast Antarctica coverage. First, the imaging time window is forecasted within the specified imaging time range to obtain all the visible time windows of the imaging satellite to Antarctica. Then, taking the selection of each time window and the satellite swing angle in each time window as decision variables, and the satellite attitude maneuver ability as constraint, an imaging mission model including two objective functions with minimum number of imaging time windows and the maximum coverage rate is established. To solving the proposed multi-objective optimization model, an improved real-binary hybrid LMOCSO (large-scale multi-objective optimization based on a competitive swarm optimizer) is proposed in this paper. Finally, a simulation experiment was performed using Gaofen-3 satellite to verify the effectiveness of the proposed method.

64Cu-DOTATATE PET in Patients with Neuroendocrine Neoplasms: Prospective, Head-to-Head Comparison of Imaging at 1 Hour and 3 Hours After Injection

64Cu-DOTATATE PET/CT imaging 1 h after injection is excellent for lesion detection in patients with neuroendocrine neoplasms (NENs). We hypothesized that the imaging time window can be extended up to 3 h after injection without significant differences in the number of lesions detected. Methods: From a prospective study, we compared, on a head-to-head basis, sets of 64Cu-DOTATATE PET/CT images from 35 patients with NENs scanned 1 and 3 h after injection of 200 MBq of 64Cu-DOTATATE. The number of lesions on both PET scans was counted and grouped according to organs or regions and compared with negative binomial regression. Discordant lesions (visible on only the 1-h images or only the 3-h 64Cu-DOTATATE PET images) were considered true if found on simultaneous CT or later MR, CT, or somatostatin receptor imaging. We measured lesion SUVmax, reference normal-organ or -tissue SUVmean, and tumor-to-normal-tissue ratios calculated from SUVmax and SUVmean Results: We found 822 concordant lesions (visible on both 1-h and 3-h 64Cu-DOTATATE PET) and 5 discordant lesions, of which 4 were considered true. One discordant case in 1 patient involved a discordant organ system (lymph node) detected on 3-h but not 1-h 64Cu-DOTATATE PET that did not alter the patient's disease stage (stage IV) because the patient had 11 additional concordant liver lesions. We found no significant differences between the number of lesions detected on 1-h and 3-h 64Cu-DOTATATE PET. Throughout the 1- to 3-h imaging window, the mean tumor-to-normal-tissue ratio remained high in all key organs: liver (1 h: 12.6 [95% confidence interval (CI), 10.2-14.9]; 3 h: 11.0 [95%CI, 8.7-13.4]), intestines (1 h: 24.2 [95%CI, 14.9-33.4]; 3 h: 28.2 [95%CI, 16.5-40.0]), pancreas (1 h: 42.4 [95%CI, 12.3-72.5]; 3 h: 41.1 [95%CI, 8.7-73.4]), and bone (1 h: 103.0 [95%CI, 38.6-167.4]; 3 h: 124.2 [95%CI, 57.1-191.2]). Conclusion: The imaging time window of 64Cu-DOTATATE PET/CT for patients with NENs can be expanded from 1 h to 1-3 h without significant differences in the number of lesions detected.

Nitroxide-radicals-modified gold nanorods for in vivo CT/MRI-guided photothermal cancer therapy.

PurposeThis article presents a report of the synthesis, characterization, and biomedical application of nitroxide-radicals–modified gold nanorods (Au-TEMPO NRs) for imaging-guided photothermal cancer therapy.Patients and methodsAu nanorods were synthesized through seed-mediated growth method, 4-Amino-TEMPO was added and the reaction proceeded under magnetic stirring.ResultsWith a mean length of 39.2 nm and an average aspect ratio of approximately 3.85, Au-TEMPO NRs showed good photothermal ability when they were irradiated by 808-nm laser. Au-TEMPO NRs could be stored in PBS for more than 1 month, showed no cytotoxicity against both tumor and normal cells at a concentration of up to 3 mg/mL, and functioned as a dual-mode contrast agent for CT/magnetic resonance (MR) imaging in vitro and in vivo, due to their high X-ray attenuation of Au and good r1 relaxivity of nitroxide radicals. Further, they had a long retention time (~4 hours) in the main organs, which enabled a long CT/MR imaging time window for diagnosis. Bio-distribution results revealed that these Au-TEMPO NRs passively aggregated in the liver and spleen. After irradiation by 808-nm laser, Au-TEMPO NRs could ablate the solid tumor in 4T1 tumor-bearing mice, which implied they were a potential theranostic agent for dual-mode imaging and photothermal cancer therapy.ConclusionThis type of Au-TEMPO NRs with the abilities of CT/MR imaging and photothermal therapy, can play an active role in imaging-guided photothermal cancer therapy.

Dynamic diffusion‐weighted hyperpolarized 13C imaging based on a slice‐selective double spin echo sequence for measurements of cellular transport

To develop a pulse sequence to dynamically measure the ADC of hyperpolarized substrates during their perfusion, metabolic conversion, and transport. We proposed a slice-selective double spin echo sequence for dynamic hyperpolarized 13 C diffusion-weighted imaging. The proposed pulse sequence was optimized for a high field preclinical scanner through theoretical analysis and simulation. The performance of the method was compared to non-slice-selective double spin echo via in vivo studies. We also validated the sequence for dynamic ADC measurement in both phantom studies and transgenic mouse model of prostate cancer studies. The optimized pulse sequence outperforms the traditional sequence with smaller saturation effects on the magnetization of hyperpolarized compounds that allowed more dynamic imaging frames covering a longer imaging time window. In pre-clinical studies (N = 8), the dynamic hyperpolarized lactate ADC maps of 6 studies in the prostate tumors showed an increase measured ADC over time, which might be related to lactate efflux from the tumor cells. The proposed sequence was validated and shown to improve dynamic diffusion weighted imaging compared to the traditional double spin echo sequence, providing ADC maps of lactate through time.

18F-Alanine Derivative Serves as an ASCT2 Marker for Cancer Imaging.

Amino acids derivative are well established molecular probes for diagnosis of a variety of cancer using positron emission tomography (PET). Recently, boramino acid (BAAs) was found as a prospective molecular platform for developing PET tracer. The objective of this study was to develop a 18F-labeled alanine derivative through displacing its carboxylate by trifluoroborate as a selective ASCT2 marker for cancer imaging. 18F-Ala-BF3 was first evaluated in healthy FVB/N mice in vivo, exhibiting rapid renal clearance with almost negligible uptake in stomach (1.53 ± 0.31%ID/g). Notable uptake was observed in thyroid (3.71 ± 0.49%ID/g, 40 min post injection), of which the uptake was significantly inhibited by co-injection with natural L-alanine. In addition, we further established 18F-Ala-BF3 on a human gastric cancer cell (BGC-823) xenografts bearing mouse model. Dynamic PET-CT scan revealed the optimal time window for tumor imaging, it was between 40 and 60 min post injection, when the BGC-823 xenografts uptake was 5.49 ± 1.47%ID/g ( n = 4), and the tumor-to-stomach, tumor-to-blood, tumor-to-muscle, and tumor-to-brain ratios were 3.27 ± 1.53, 3.80 ± 1.48, 3.47 ± 1.48, and 6.20 ± 1.47, respectively.

Time-frequency analysis-based time-windowing algorithm for the inverse synthetic aperture radar imaging of ships

An algorithm based on time-frequency analysis is proposed to select an imaging time window for the inverse synthetic aperture radar imaging of ships. An appropriate range bin is selected to perform the time-frequency analysis after radial motion compensation. The selected range bin is that with the maximum mean amplitude among the range bins whose echoes are confirmed to be contributed by a dominant scatter. The criterion for judging whether the echoes of a range bin are contributed by a dominant scatter is key to the proposed algorithm and is therefore described in detail. When the first range bin that satisfies the judgment criterion is found, a sequence composed of the frequencies that have the largest amplitudes in every moment’s time-frequency spectrum corresponding to this range bin is employed to calculate the length and the center moment of the optimal imaging time window. Experiments performed with simulation data and real data show the effectiveness of the proposed algorithm, and comparisons between the proposed algorithm and the image contrast-based algorithm (ICBA) are provided. Similar image contrast and lower entropy are acquired using the proposed algorithm as compared with those values when using the ICBA.

ROI-ORIENTATED SENSOR CORRECTION BASED ON VIRTUAL STEADY REIMAGING MODEL FOR WIDE SWATH HIGH RESOLUTION OPTICAL SATELLITE IMAGERY

Abstract. To meet the requirement of high accuracy and high speed processing for wide swath high resolution optical satellite imagery under emergency situation in both ground processing system and on-board processing system. This paper proposed a ROI-orientated sensor correction algorithm based on virtual steady reimaging model for wide swath high resolution optical satellite imagery. Firstly, the imaging time and spatial window of the ROI is determined by a dynamic search method. Then, the dynamic ROI sensor correction model based on virtual steady reimaging model is constructed. Finally, the corrected image corresponding to the ROI is generated based on the coordinates mapping relationship which is established by the dynamic sensor correction model for corrected image and rigours imaging model for original image. Two experimental results show that the image registration between panchromatic and multispectral images can be well achieved and the image distortion caused by satellite jitter can be also corrected efficiently.

Intraoperative Localization of Rectal Tumors Using Liposomal Indocyanine Green.

Tumor localization may pose a significant challenge during minimally invasive rectal resection. Near-infrared (NIR) imaging can penetrate biological tissue and afford tumor localization from the external surface of the rectum. Our aim was to develop an NIR-based tool for rectal tumor imaging that can be administered intravenously. We prepared indocyanine-green (ICG)-loaded liposomes by sonication. Liposomes were evaluated for their size and morphology. We then used an endoscopically induced rectal cancer in mice as a model for rectal cancer. After intravenous administration, tumors were evaluated for their fluorescence intensity. Tumor intensity was expressed in relation to the background signal, that is, tumor to background ratio (TBR). Liposomes in various sizes could be prepared by adjusting sonication time. We selected 100-nm-sized liposomes for further experiments. Transmission electron microscopy showed spherical particles and confirmed the size measurements. The liposomes could be lyophilized and then rehydrated again before use without compromising their structure or signal. Fluorescence intensity was kept for 24 hours after solubilization. Testing the optimal time course for rectal tumor imaging revealed that early time course (up to 3 hours) yielded nonspecific imaging, whereas after long time course (24 hours), a very weak signal remained in the tissue. The optimal time window for imaging was after 12 hours from injection, with TBR = 8.1 ± 3.6 ( P = .002). Free ICG could not achieve similar results. The liposomal ICG can be reproducibly prepared and kept in lyophilized form. Liposomal ICG could serve as a tool for intraoperative tumor localization.

Hypothermia-treated neonates with hypoxic-ischemic encephalopathy: Optimal timing of quantitative ADC measurement to predict disease severity.

To determine the optimal time window for MR imaging with quantitative ADC measurement in neonatal HIE after hypothermia treatment, a retrospective review was performed on consecutive hypothermia-treated term neonates with HIE, with an initial and follow-up MR imaging within the first two weeks of life. Three neuroradiologists categorized each set of MR imaging as normal, mild, moderate or severe HIE based on a consensus review of the serial imaging. The lowest ADC values from the white matter, corpus callosum, and basal ganglia/thalamus were measured. The ADC values between mild-moderate and severe HIE were compared using a Student's t-test over a range of different time windows. A total of 33 MR imaging examinations were performed on 16 neonates that included three normal, four mild, five moderate, and four severe HIE. The time window of 3-10 days showed a statistically significant decrease in ADC value in severe HIE compared to mild-moderate HIE in all three locations, respectively: white matter 0.5 ± 0.22 versus 0.83 ± 0.27 ( p value 0.01), corpus callosum 0.69 ± 0.19 versus 0.91 ± 0.17 ( p value 0.01), and basal ganglia/thalamus 0.63 ± 0.16 versus 0.98 ± 0.06 ( p value <0.01). The range of 3-10 days is the optimal time window for MR imaging with quantitative ADC after hypothermia treatment.

A stress-related explanation to the increased blood pressure and its course following ischemic stroke

BackgroundA hypertensive response after ischemic stroke is frequent, yet its pathophysiology is unknown. Mechanisms related to local ischemic damage, major vascular occlusion, and psychological stress due to acute illness have been proposed. We assessed the natural course of blood pressure (BP) within the first 24 h in groups of ischemic stroke patients with different characteristics. We hypothesized that a consistent BP reduction, regardless of stroke location, time window from debut to admission and presence of persistent vascular occlusion, would favor a stress-related mechanism as an important cause of the hypertensive response after ischemic stroke.MethodsIschemic stroke patients (n=1067) were prospectively registered, and BP was measured on admission and <3 h, 3–6 h, 6–12 h and 12–24 h after admission. Patients were categorized according to the location of diffusion-weighted imaging (DWI) lesions (cortical, large subcortical, mixed cortico-subcortical, lacunar, cerebellar, brain stem or multiple), time window (admitted within or after 6 h of symptom onset) and presence of persistent proximal middle cerebral artery (MCA) occlusion versus normal findings on magnetic resonance angiography (MRA) at 24 h.ResultsA reduction in systolic BP and diastolic BP from baseline to 12–24 h was found across all DWI locations except for diastolic BP in cerebellar (P=0.072) lesions. Apart from diastolic BP in patients with normal MRA findings at 24 h (P=0.060), a significant fall in systolic BP and diastolic BP at 12–24 h was registered, irrespective of whether patients were admitted within 6 h or after 6 h of stroke onset or had persistent MCA occlusion versus normal MRA findings.ConclusionWe found a relatively consistent decline in BP within 24 h after admission across different stroke locations in patients admitted within or after 6 h of stroke onset and in patients with persistent MCA occlusion. Our findings suggest that a systemic factor such as psychological stress may be an important contributor to the frequently elevated BP on admission in patients with ischemic stroke.

A Novel Tumor-Specific Agent for Intraoperative Near-Infrared Fluorescence Imaging: A Translational Study in Healthy Volunteers and Patients with Ovarian Cancer.

Completeness of cytoreductive surgery is a key prognostic factor for survival in patients with ovarian cancer. The ability to differentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this differentiation is often difficult and can lead to incomplete tumor removal. Near-infrared fluorescence imaging has the potential to improve the detection of malignant tissue during surgery, significantly improving outcome. Here, we report the use of OTL38, a near-infrared (796 nm) fluorescent agent, that binds folate receptor alpha, which is expressed in >90% of epithelial ovarian cancers. We first performed a randomized, placebo-controlled study in 30 healthy volunteers. Four single increasing doses of OTL38 were delivered intravenously. At fixed times following drug delivery, tolerability and blood/skin pharmacokinetics were assessed. Next, using the results of the first study, three doses were selected and administered to 12 patients who had epithelial ovarian cancer and were scheduled for cytoreductive surgery. We measured tolerability and blood pharmacokinetics, as well as the ability to detect the tumor using intraoperative fluorescence imaging. Intravenous infusion of OTL38 in 30 healthy volunteers yielded an optimal dosage range and time window for intraoperative imaging. In 12 patients with ovarian cancer, OTL38 accumulated in folate receptor alpha-positive tumors and metastases, enabling the surgeon to resect an additional 29% of malignant lesions that were not identified previously using inspection and/or palpation. This study demonstrates that performing real-time intraoperative near-infrared fluorescence imaging using a tumor-specific agent is feasible and potentially clinically beneficial. Clin Cancer Res; 22(12); 2929-38. ©2016 AACR.

High-Performance Upconversion Nanoprobes for Multimodal MR Imaging of Acute Ischemic Stroke.

Multimodal magnetic resonance (MR) imaging, including MR angiography (MRA) and MR perfusion (MRP), plays a critical role in the diagnosis and surveillance of acute ischemic stroke. However, these techniques are hindered by the low T1 relaxivity, short circulation time, and high leakage rate from vessels of clinical Magnevist. To address these problems, nontoxic polyethylene glycol (PEG)ylated upconversion nanoprobes (PEG-UCNPs) are synthesized and first adopted for excellent MRA and MRP imaging, featuring high diagnostic sensitivity toward acute ischemic stroke in high-resolution imaging. The investigations show that the agent possesses superior advantages over clinical Magnevist, such as much higher relaxivity, longer circulation time, and lower leakage rate, which guarantee much better imaging efficiency. Remarkably, an extremely small dosage (5 mg Gd kg(-1) ) of PEG-UCNPs provides high-resolution MRA imaging with the vascular system delineated much clearer than the Magnevist with clinical dosage as high as 108 mg Gd kg(-1) . On the other hand, the long circulation time of PEG-UCNPs enables the surveillance of the progression of ischemic stroke using MRA or MRP. Once translated, these PEG-UCNPs are expected to be a promising candidate for substituting the clinical Magnevist in MRA and MRP, which will significantly lengthen the imaging time window and improve the overall diagnostic efficiency.

Preparation of linear poly(glycerol) as a T1 contrast agent for tumor-targeted magnetic resonance imaging.

Macromolecular contrast agents (CAs) labeled with targeting molecules are gaining remarkable interest as promising materials overcoming the defects of small-molecule CAs. Designed on the basis of biocompatible poly(glycerol) (PG), a linear macromolecular contrast agent (CA) was synthesized with a composition of PG as a backbone and partial hydroxyl connected with gadolinium labeled poly(l-lysine) dendrons, where folic acid was also conjugated. This linear CA exhibited higher relaxivity (7.04 mM-1 S-1) relative to Magnevist® (3.98 mM-1 S-1), and showed negligible toxicity determined by WST assay and histological analysis. In vitro and in vivo magnetic resonance imaging (MRI) measurements presented obvious target specificity to KB cells and tumor. Moreover, high signal enhancement was observed in the tumor region at various time points after intravenous injection to ensure the long time window for imaging. All the findings make it an attractive candidate for tumor-targeted MRI CAs.

High-contrast Noninvasive Imaging of Kidney Clearance Kinetics Enabled by Renal Clearable Nanofluorophores.

Noninvasive imaging of kidney clearance kinetics (KCK) of renal clearable probes is key to studying unilateral kidney function diseases, but such imaging is highly challenging to achieve with in vivo fluorescence. While this long-standing challenge is often attributed to the limited light penetration depth, we found that rapid and persistent accumulation of conventional dyes in the skin "shadowed" real fluorescence signals from the kidneys and prevented noninvasive imaging of KCK, which, however, can be addressed with renal clearable nanofluorophores. By integrating near infrared emission with efficient renal clearance and ultralow background interference, the nanofluorophores can increase kidney-contrast enhancement and imaging-time window by approximately 50- and 1000-fold over conventional dyes, and significantly minimize deviation between noninvasive and invasive KCK, laying down a foundation for translating in vivo fluorescence imaging in preclinical noninvasive kidney function assessments.