Separating spin compartments in arterial spin labeling using delays alternating with nutation for tailored excitation (DANTE) pulse: A validation study using T2 -relaxometry and application to arterial cerebral blood volume imaging.

PURPOSE: To clarify the type of spin compartment in arterial spin labeling (ASL) that is eliminated by delays alternating with nutation for tailored excitation (DANTE) pulse using T2 -relaxometry, and to demonstrate the feasibility of arterial cerebral blood volume (CBVa ) imaging using DANTE-ASL in combination with a simplified two-compartment model. METHOD: The DANTE and T2 -preparation modules were combined into a single ASL sequence. T2 values under the application of DANTE were determined to evaluate changes in T2 , along with the post-labeling delay (PLD) and the relationship between transit time without DANTE (TTnoVS ) and T2 . The reference tissue T2 (T2_ref ) was also obtained. Subsequently, the DANTE module was embedded into the Hadamard-encoded ASL. Cerebral blood flow (CBF) and CBVa were computed using two Hadamard-encoding datasets (with and without DANTE) in a rest and breath-holding (BH) task. RESULTS: While T2 without DANTE (T2_noVS ) decreased as the PLD increased, T2 with DANTE (T2_DANTE ) was equivalent to T2_ref and did not change with the PLD. Although there was a significant positive correlation between TTnoVS and T2_noVS with short PLD, T2_DANTE was not correlated with TTnoVS nor PLD. Baseline CBVa values obtained at rest were 0.64 ± 0.12, 0.64 ± 0.11, and 0.58 ± 0.15 mL/100 g for anterior, middle, and posterior cerebral arteries, respectively. Significant CBF and CBVa elevations were observed in the BH task. CONCLUSION: Microvascular compartment signals were eliminated from the total ASL signals by DANTE. CBVa can be measured using Hadamard-encoded DANTE-ASL in combination with a simplified two-compartment model.

Robust arterial transit time and cerebral blood flow estimation using combined acquisition of Hadamard-encoded multi-delay and long-labeled long-delay pseudo-continuous arterial spin labeling: a simulation and in vivo study.

Arterial transit time (ATT) prolongation causes an error of cerebral blood flow (CBF) measurement during arterial spin labeling (ASL). To improve the accuracy of ATT and CBF in patients with prolonged ATT, we propose a robust ATT and CBF estimation method for clinical practice. The proposed method consists of a three-delay Hadamard-encoded pseudo-continuous ASL (H-pCASL) with an additional-encoding and single-delay with long-labeled long-delay (1dLLLD) acquisition. The additional-encoding allows for the reconstruction of a single-delay image with long-labeled short-delay (1dLLSD) in addition to the normal Hadamard sub-bolus images. Five different images (normal Hadamard 3 delay, 1dLLSD, 1dLLLD) were reconstructed to calculate ATT and CBF. A Monte Carlo simulation and an in vivo study were performed to access the accuracy of the proposed method in comparison to normal 7-delay (7d) H-pCASL with equally divided sub-bolus labeling duration (LD). The simulation showed that the accuracy of CBF is strongly affected by ATT. It was also demonstrated that underestimation of ATT and CBF by 7d H-pCASL was higher with longer ATT than with the proposed method. Consistent with the simulation, the 7d H-pCASL significantly underestimated the ATT compared to that of the proposed method. This underestimation was evident in the distal anterior cerebral artery (ACA; P = 0.0394) and the distal posterior cerebral artery (PCA; 2 P = 0.0255). Similar to the ATT, the CBF was underestimated with 7d H-pCASL in the distal ACA (P = 0.0099), distal middle cerebral artery (P = 0.0109), and distal PCA (P = 0.0319) compared to the proposed method. Improving the SNR of each delay image (even though the number of delays is small) is crucial for ATT estimation. This is opposed to acquiring many delays with short LD. The proposed method confers accurate ATT and CBF estimation within a practical acquisition time in a clinical setting.

Intravascular signal suppression and microvascular signal mapping using delays alternating with nutation for tailored excitation (DANTE) pulse for arterial spin labeling perfusion imaging.

OBJECTIVE: To optimize the delays alternating with nutation for tailored excitation (DANTE) pulse as a vascular crushing gradient to eliminate macro-and micro-vascular signals and to generate a macrovascular space-related map by applying DANTE with multiple conditions. MATERIALS AND METHODS: Numerical simulation was performed to estimate the optimal flip angle (FA) of the DANTE. A phantom study was conducted to evaluate the impact of the FA and gradient area (GA) of the DANTE with three flow velocities and various parameters of the DANTE. Finally, an in vivo study was performed to assess the optimal DANTE parameters and to map the estimated macrovascular signal of the arterial spin labeling (ASL) signal. RESULTS: Numerical simulation revealed that the decrease of magnetization plateaued at 12.5° of FA. The phantom study showed that the setting of larger FA or GA decreased the ASL signals. The decrease of the ASL signal depended on the flow velocity, and the dependence increased with decreasing GA. The in vivo study revealed that larger FA and GA decreased the perfusion signal. DISCUSSION: An optimized DANTE makes it possible to efficiently suppress the macro-and-micro vascular signals depending on the flow velocity. Moreover, macrovascular signal mapping may be useful to assess altered hemodynamic states.

[Simplification of Activity Measurement during Quantitative Value Estimation in Bone SPECT].

PURPOSE: To calculate the quantitative values in bone single-photon emission computed tomography, it is necessary to measure the amount of syringe radiation before and after the administration of a radiopharmaceutical. We proposed a method to omit the measurement of radioactivity. In this study, we clarified the effects of adopting this method and calculated its influence on quantitative values in a clinical setting. METHODS: We derived a relational expression of the administration time and dose of radioactivity from the measured value and the administration time of the syringe dose before and after the administration in each patient. Next, we determined the differences for radioactivity calculated from this relational expression (estimated dose) and actual administered radioactivity (actual dose). Furthermore, we calculated the differences in the quantitative values of a normal region (the fourth lumbar vertebra) on adopting these data. RESULTS: No significant differences between the estimated dose and actual dose were noted. Additionally, no significant differences in the quantitative values were observed. CONCLUSION: Our findings suggest that adoption of the estimated dose does not affect the quantitative value. When the estimated dose is adopted, it can be administered with an accuracy of 0.80%. Thus, it is possible to omit the actual measurement of radioactivity by using our proposed method.

Evaluation of retained products of conception using pulsed continuous arterial spin-labeling MRI: clinical feasibility and initial results.

OBJECTIVES: We evaluated the vascularity of retained products of conception (RPOC) using arterial spin-labeling magnetic resonance imaging (ASL-MRI) to clarify the clinical feasibility of this approach. MATERIALS AND METHODS: A pulsed-continuous ASL sequence with echo-planar imaging (EPI) acquisitions was used. Ten consecutive patients with RPOC were enrolled. All ASL images were evaluated visually and semiquantitatively and compared with the findings of Doppler ultrasound (US) and dynamic contrast-enhanced MRI (DCE-MRI). RESULTS: The technical success rate was 93.7% (15/16 scans). One failed case was excluded from the analysis. Six patients showed quite high signals over RPOC, while three patients showed no abnormal signals. Doppler US alone failed to detect the hypervascular area in two cases, and ASL-MRI alone failed in three. A significant linear correlation was found between semiquantitative values of ASL-MRI and DCE-MRI. All six patients showing high signals on ASL-MRI underwent follow-up MRI after therapy. High signals in five patients decreased visually and semiquantitatively, while one patient showed signal increases. CONCLUSION: Evaluation of RPOC using ASL-MRI was clinically feasible and response to therapy could be evaluated. However, the clinical advantages over conventional imaging remain unclear and need to be evaluated.

Simultaneous acquisition of high-contrast and quantitative liver T1 images using 3D phase-sensitive inversion recovery: a feasibility study.

Background Tumor-to-liver contrast is low in images of chronically diseased livers because gadolinium-based hepatocyte-specific contrast agents (Gd-EOB-DTPA) accumulate less to hepatocytes. Purpose To determine whether phase-sensitive inversion recovery (PSIR) could improve the T1 contrasts of Gd-based contrast agents and liver parenchyma and simultaneously provide accurate T1 values for abdominal organs. Material and Methods The image contrasts of phantoms with different Gd concentrations that were obtained using PSIR were compared to conventional turbo field echo (TFE) results. T1 value was estimated using PSIR by performing iterations to investigate the two IR magnetization evolutions. The estimated T1 values were validated using IR-spin echo (IR-SE) and Look-Locker (L-L) sequences. In an in vivo study, the liver-to-spleen and liver-to-muscle contrasts of the PSIR and TFE images of seven volunteers were compared, as were the T1 values of liver parenchyma, spleen, and muscle obtained using PSIR and L-L sequences. Results The PSIR images showed T1 contrasts higher than those in the TFE results. The PSIR and IR-SE T1 values were linearly correlated. Additionally, the R1 estimated using PSIR were correlated with those measured using IR-SE and L-L. In the in vivo study, the liver-to-spleen and liver-to-muscle contrasts of PSIR were significantly higher than those obtained using TFE. T1 values of abdominal organs obtained using PSIR and L-L were clearly correlated. Conclusion PSIR may be capable of improving liver image T1 contrasts when Gd-based contrast agents are employed and simultaneously yielding accurate T1 values of abdominal organs.

Comparison of long-labeled pseudo-continuous arterial spin labeling (ASL) features between young and elderly adults: special reference to parameter selection.

BACKGROUND: The signal intensity obtained by arterial spin labeling (ASL) depends not only on perfusion signal, but also on arterial transit time (ATT). Although ATT has a more significant effect on accurate regional cerebral blood flow (CBF) calculations, the multiple post-labeling delay (PLD) approach is difficult to use in routine examinations. PURPOSE: To optimize imaging parameters for labeling duration (LD) and PLD and to confirm their validity in long-labeled pseudo-continuous ASL. MATERIAL AND METHODS: The perfusion signal was simulated in four LDs and theoretical signal-to-noise ratio efficiency (SNReff) was calculated. In vivo studies were performed on a 3.0 T magnetic resonance imaging (MRI) scanner and 15 volunteers were categorized into either the young or elderly adult groups. We compared the differences in CBF values with or without ATT correction. RESULTS: Regarding signal simulation, perfusion signal increased with the length of LD. SNReff also improved with LD, but SNReff plateaued at an LD of 3.0 s. As for the in vivo study, SNR linearly increased along with the LD. The CBF differences with the correction of ATT were larger in the elderly adult group. This trend was most prominent in the longer ATT area in the occipital cortical region. CONCLUSION: A combination of imaging settings of LD = 3.5 s and PLD = 2.0 s were suggested as optimal imaging parameters for allowing acceptable CBF quantification and sufficient SNR in both young and elderly individuals.

Evaluation of obliteration of arteriovenous malformations after stereotactic radiosurgery with arterial spin labeling MR imaging.

PURPOSE: Complete obliteration of treated arteriovenous malformations (AVMs) can be diagnosed only by confirming the disappearance of arterio-venous (A-V) shunts with invasive catheter angiography. The authors evaluated whether non-invasive arterial spin labeling (ASL) magnetic resonance (MR) imaging can be used to diagnose the obliteration of AVMs facilitate the diagnosis of AVM obliteration after treatment with stereotactic radiosurgery (SRS). MATERIAL AND METHODS: Seven patients with a cerebral AVM treated by SRS were followed up with ASL images taken with a 3T-MR unit, and received digital subtraction angiography (DSA) after the AVM had disappeared on ASL images. Three patients among the seven received DSA also after the postradiosurgical AVM had disappeared on conventional MR images but A-V shunt was residual on ASL images. Four patients among the seven received contrast-enhanced (CE) MR imaging around the same period as DSA. RESULTS: ASL images could visualize postradiosurgical residual A-V shunts clearly. In all seven patients, DSA after the disappearance of A-V shunts on ASL images demonstrated no evidence of A-V shunts. In all three patients, DSA after the AVM had disappeared on conventional MR images but not on ASL images demonstrated residual A-V shunt. CE MR findings of AVMs treated by SRS did not correspond with DSA findings in three out of four patients. CONCLUSIONS: Findings of radiosurgically treated AVMs on ASL images corresponded with those on DSA. The results of this study suggest that ASL imaging can be utilized to follow up AVMs after SRS and to decide their obliteration facilitate to decide the precise timing of catheter angiography for the final diagnosis of AVM obliteration after SRS.

Standardized uptake value differences between primary and metastatic lesions in ¹8F-FDG PET/CT of patients with lung cancer.

BACKGROUND: FDG-PET/CT is a robust tool for staging of lung cancer, but the differences in FDG uptake between primary and metastatic lesions have not yet been well described. PURPOSE: To define the potential range of standardized uptake value (SUV) differences between primary and metastatic lesions in lung cancer patients and to identify the factors responsible for these differences. MATERIAL AND METHODS: FDG-PET/CT images of 75 lung cancers with 296 metastases were analyzed retrospectively. Histological types, primary locations, and metastatic sites were recorded. The average and maximum SUV (SUVavg, SUVmax) of each primary tumor and metastasis were measured, and the ratio of metastatic SUVs to primary SUVs (M/Pavg, M/Pmax), its difference from 100% (diff-M/Pavg, diff-M/Pmax), the ratio of ROI area of metastatic to primary lesions (ROI-M/P), and its difference from 100% (diff-ROI-M/P) were calculated. RESULTS: M/Pavg was in the range of 35.9-224.6% (mean ± SD: 97.9% ± 35.9%), while M/Pmax was in the range of 24.8-286.7% (98.1% ± 45.3%). Furthermore, values were in the range of 50-200% for M/Pavg in 280/296 lesions (94.6%) and for M/Pmax in 255/296 lesions (86.1%). M/Pavg and M/Pmax showed significant linear correlations with ROI-M/P (r = 0.62, 0.64, respectively). Multivariate analysis showed that diff-ROI-M/P had the greatest effect on diff-M/Pavg and diff-M/Pmax. CONCLUSION: The SUVs of most metastatic lesions ranged from half to double those of primaries in lung cancer patients. When the SUV of a suspected metastasis is beyond the range of half to double that of the primary lung cancer, other non-metastatic lesions should be considered, while taking ROI size into account.

Serial changes of (18)F-FDG PET/CT findings in ischiopubic synchondrosis: comparison with contrast-enhanced MRI.

UNLABELLED: A 3 years old female patient underwent resection and chemotherapy for a yolk sac tumor of the retroperitoneum. Two years later, fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) showed high uptake in the right ischiopubic synchondrosis (IPS), which had a radiolucent structure on CT. The structure showed contrast enhancement on magnetic resonance imaging (MRI), which was a non-specific finding. Six weeks later, a follow-up (18)F-FDG PET/CT scan was performed which showed no abnormal uptake in the IPS. The disappearance of (18)F-FDG uptake preceded that of contrast enhancement on MRI, which was seen 7 months after the initial (18)F-FDG PET/CT scan. CONCLUSION: This is the first report showing serial changes of (18)F-FDG uptake in IPS, in comparison to MRI findings.

[Development of an magnetic resonance imaging safety management system for metallic biomedical products using an magnetic resonance compatibility database and inquiry-based patient records].

Several incidents involving magnetic resonance imaging (MRI) examinations of patients with unchecked MR-unsafe metallic products have been reported. To improve patient safety, we developed a new MRI safety management system for metallic biomedical products and evaluated its efficiency in clinical practice. Our system was integrated into the picture archiving and communication system (PACS) and comprised an MR compatibility database and inquiry-based patient records of internal metallic biomedical products, enabling hospital staff to check MR compatibility by product name. A total of 6,637 biomedical implants and devices were listed in this system, including product names and their MR compatibilities. Furthermore, MRI histories for each patient at our hospital were also recorded. Using this system, it was possible to confirm the MR compatibility of the patients' metallic biomedical products effectively and to reduce the number of unchecked internal products through systematic patient inquiry. In conclusion, our new system enhanced metallic biomedical product checking procedures, and improved patient safety during clinical MRI examinations.

Fluorescence endoscopic detection of murine colitis-associated colon cancer by topically applied enzymatically rapid-activatable probe.

OBJECTIVES: Screening colonoscopy to monitor for early colitis-associated colon cancer (CAC) is difficult due to the aberrant mucosal patterns associated with long-standing colitis. The aim of this study was to develop a rapid fluorescent detection method for use during colonoscopy for improving the detection of CAC utilising a topically applied enzymatically activatable probe (gGlu-HMRG) which fluoresces in the presence of γ-glutamyltranspeptidase (GGT), an enzyme associated with cancer. METHODS: Expression of GGT in colon cell lines was examined with fluorescence microscopy and flow cytometry. A mouse model (azoxymethane/dextran sulphate sodium) of CAC was used and mice were examined with white light and fluorescence colonoscopy before and after topical gGlu-HMRG administration. RESULTS: Expression of GGT, although variable, was higher in human colon cancer cells than normal human colon cells. Using fluorescence colonoscopy in mice, gGlu-HMRG fluorescent lesions were detected 5 min after topical administration and fluorescence persisted for at least 30 min. Fluorescence guided biopsy revealed all fluorescent lesions that contained cancer or dysplasia (n=16), whereas three out of 12 non-fluorescent lesions contained low grade dysplasia and others did not contain neoplastic histology. Microscopic inflammatory infiltration also had variable fluorescence but in general was much lower (∼10-fold) in signal than cancer. Repeat fluorescence endoscopy allowed individual tumours to be monitored. CONCLUSION: These results suggest that gGlu-HMRG can improve endoscopic detection of CAC with a higher target to background ratio than conventional white light colonoscopy. This could be of benefit to patients with long-standing colitis who must undergo repeated screening colonoscopies.

A rare congenital anomaly, bridge-like appendiceal fistula to the terminal ileum, demonstrated by MDCT.

Although appendiceal anatomical anomalies are very rare, understanding of the anatomical details of these anomalies is important for surgery. In this case report, we present images from multi-detector row computed tomography (MDCT) and histological findings of a rare anatomical appendiceal anomaly originating from the cecum and opening into the terminal ileum like a bridge. These anatomical details were clearly depicted on MDCT with multi-planar reconstruction. MDCT demonstrated a communication between the appendix and terminal ileum. Histological analysis revealed that a normal mucosal layer was maintained from the appendix to the connected ileum, without any evidence of inflammatory or neoplastic changes, and only thickening of the muscular layer of the appendix was identified. Based on these histological findings, the appendix was considered to represent an anatomical anomaly rather than secondary fistula caused by inflammation or neoplasm, which has not yet been reported.

Specific Binding Ratio Estimation of [123I]-FP-CIT SPECT Using Frontal Projection Image and Machine Learning.

This study aimed to develop a new convolutional neural network (CNN) method for estimating the specific binding ratio (SBR) from only frontal projection images in single-photon emission-computed tomography using [123I]ioflupane. We created five datasets to train two CNNs, LeNet and AlexNet: (1) 128FOV used a 0° projection image without preprocessing, (2) 40FOV used 0° projection images cropped to 40 × 40 pixels centered on the striatum, (3) 40FOV training data doubled by data augmentation (40FOV_DA, left-right reversal only), (4) 40FOVhalf, and (5) 40FOV_DAhalf, split into left and right (20 × 40) images of 40FOV and 40FOV_DA to separately evaluate the left and right SBR. The accuracy of the SBR estimation was assessed using the mean absolute error, root mean squared error, correlation coefficient, and slope. The 128FOV dataset had significantly larger absolute errors compared to all other datasets (p < 0. 05). The best correlation coefficient between the SBRs using SPECT images and those estimated from frontal projection images alone was 0.87. Clinical use of the new CNN method in this study was feasible for estimating the SBR with a small error rate using only the frontal projection images collected in a short time.

The Utility of Arterial Transit Time Measurement for Evaluating the Hemodynamic Perfusion State of Patients with Chronic Cerebrovascular Stenosis or Occlusive Disease: Correlative Study between MR Imaging and 15O-labeled H2O Positron Emission Tomography.

PURPOSE: To verify whether arterial transit time (ATT) mapping can correct arterial spin labeling-cerebral blood flow (ASL-CBF) values and to verify whether ATT is a parameter that correlates with positron emission tomography (PET)-oxygen extraction fraction (OEF) and PET-mean transit time (MTT). METHODS: Eleven patients with unilateral major cerebral artery stenosis or occlusion underwent MRI and PET in the chronic or asymptomatic phase. ASL-MRI acquisitions were conducted with each of two post-label delay (PLD) settings (0.7s and 2.0s) using a pseudo-continuous ASL pulse sequence and 3D-spin echo spiral readout with vascular crusher gradient. ATT maps were obtained using a low-resolution pre-scan approach with five PLD settings. Using the ASL perfusion images and ATT mapping, ATT-corrected ASL-CBF images were obtained. Four kinds of ASL-CBF methods (PLD 0.7s with or without ATT correction and PLD 2.0s with or without ATT correction) were compared to PET-CBF, using vascular territory ROIs. ATT and OEF were compared for all ROIs, unaffected side ROIs, and affected side ROIs, respectively. ATT and MTT were compared by the ratio of the affected side to the unaffected side. Transit time-based ROIs were used for the comparison with ATT. RESULTS: Comparing ASL-CBF and PET-CBF, the correlation was higher with ATT correction than without correction, and for a PLD of 2.0s compared with 0.7s. The best correlation was for PLD of 2.0s with ATT correction (R2 = 0.547). ROIs on the affected side showed a low but significant correlation between ATT and PET-OEF (R2 = 0.141). There was a low correlation between the ATT ratio and the MTT ratio (R2 = 0.133). CONCLUSION: Low-resolution ATT correction may increase the accuracy of ASL-CBF measurements in patients with unilateral major cerebral artery stenosis or occlusion. In addition, ATT itself might have a potential role in detecting compromised hemodynamic state.

[18F]FES PET Resolves the Diagnostic Dilemma of COVID-19-Vaccine-Associated Hypermetabolic Lymphadenopathy in ER-Positive Breast Cancer.

Coronavirus disease (COVID-19) vaccination is known to cause a diagnostic dilemma due to false-positive findings on [18F]FDG PET in vaccine-associated hypermetabolic lymphadenopathy. We present two case reports of women with estrogen-receptor (ER)-positive cancer of the breast who were vaccinated for COVID-19 in the deltoid muscle. [18F]FDG positron emission tomography (PET) demonstrated primary breast cancer and multiple axillary lymph nodes with increased [18F]FDG uptake, diagnosed as vaccine-associated [18F]FDG-avid lymph nodes. Subsequent [18F]FES PET revealed single axillary lymph node metastasis in the vaccine-associated [18F]FDG-avid lymph nodes. To the best of our knowledge, this is the first study showing the usefulness of [18F]FES PET in diagnosing axillary lymph node metastasis in COVID-19-vaccinated patients harboring ER-positive breast cancer. Thus, [18F]FES PET has potential applications in the detection of true-positive metastatic lymph nodes in patients with ER-positive breast cancer regardless of the ipsilateral or contralateral side, who have received COVID-19 vaccination.

COVID-19 pneumonia detected by [18F]FDG PET/MRI: a case with negative antigen test and chest X-ray results.

Since the outbreak of pneumonia caused by a novel coronavirus (SARS-CoV-2) named Coronavirus disease 2019 (COVID-19) in China, researchers have reported the fluorodeoxyglucose positron emission tomography/CT (FDG PET/CT) manifestations of COVID-19 infection. We present a 37-year-old female with early-stage cervical cancer and fever without a focus who had negative SARS-CoV-2 antigen test and chest X-ray results. FDG PET/MRI performed for preoperative evaluation incidentally detected pneumonia showing high FDG uptake and diffusion-weighted imaging signals in right lung base. She retested positive for SARS-CoV-2 and was diagnosed as having COVID-19 pneumonia. Whole-body PET/MRI can provide multi functional images and could be useful for evaluating the pathophysiology of COVID-19.

Near infrared fluorescence-guided real-time endoscopic detection of peritoneal ovarian cancer nodules using intravenously injected indocyanine green.

Near infrared fluorescence-guidance can be used for the detection of small cancer metastases and can aid in the endoscopic management of cancer. Indocyanine green (ICG) is a Food and Drug Administration (FDA)-approved fluorescence agent. Through non-specific interactions with serum proteins, ICG achieves enhanced permeability and retention (EPR) effects. Yet, ICG demonstrates rapid clearance from the circulation. Therefore, ICG may be an ideal contrast agent for real-time fluorescence imaging of tumors. To evaluate the usefulness of real-time dual fluorescence and white light endoscopic optical imaging to detect tumor implants using the contrast agent ICG, fluorescence-guided laparoscopic procedures were performed in mouse models of peritoneally disseminated ovarian cancers. Animals were administered intravenous ICG or a control contrast agent, IR800-conjugated to albumin. The ability to detect small ovarian cancer implants was then compared. Using the dual view microendoscope, ICG clearly enabled visualization of peritoneal ovarian cancer metastatic nodules derived from SHIN3 and OVCAR5 cells at 6 and 24 hr after injection with significantly higher tumor-to-background ratio than the control agent, IR800-albumin (p < 0.001). In conclusion, ICG has the desirable properties of having both EPR effects and rapid clearance for the real-time endoscopic detection of tiny ovarian cancer peritoneal implants compared to a control macromolecular agent with theoretically better EPR effects but longer circulatory retention. Given that ICG is already FDA-approved and has a long track record of human use, this method could be easily translated to the clinic as a robust tool for fluorescence-guided endoscopic procedures for the management and treatment of cancer.

Activatable optical imaging with a silica-rhodamine based near infrared (SiR700) fluorophore: a comparison with cyanine based dyes.

Optical imaging is emerging as an important tool to visualize tumors. However, there are many potential choices among the available fluorophores. Optical imaging probes that emit in the visible range can image superficial tumors with high quantum yields; however, if deeper imaging is needed then near-infrared (NIR) fluorophores are necessary. Most commercially available NIR fluorophores are cyanine based and are prone to nonspecific binding and relatively limited photostability. Silica-containing rhodamine (SiR) fluorophores represent a new class of NIR fluorophores, which permit photoactivation via H-dimer formation as well as demonstrate improved photostability. This permits higher tumor-to-background ratios (TBRs) to be achieved over longer periods of time. Here, we compared an avidin conjugated with SiR700 (Av-SiR700) to similar compounds based on cyanine dyes (Av-Cy5.5 and Av-Alexa Fluor 680) in a mouse tumor model of ovarian cancer metastasis. We found that the Av-SiR700 probe demonstrated superior quenching, enabling activation after binding-internalization to the target cell. As a result, Av-SiR700 had higher TBRs compared to Av-Cy5.5 and better biostability compared to Av-Alexa Fluor 680.