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Rationale and Objectives High-grade gastroenteropancreatic neuroendocrine neoplasms (G3 GEP-NENs) are pathologically classified into well differentiated neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (G3 NECs). Using a novel parameter, we examined the prognostic value of 18F-FDG and 68Ga-DOTATATE PET/CT quantification in comparison to pathologic assessment in G3 GEP-NENs. Materials and Methods A total of 31 patients with G3 GEP-NENs were reviewed. For each patient, the SUVmax on 18F-FDG and 68Ga-DOTATATE PET/CT were used to calculate the FDG-DOTATATE-Z (FDZ) score: a continuous parameter that increases with 68Ga-DOTATATE uptake and decreases with 18F-FDG uptake. The variation in the FDZ score with respect to pathologic variables was examined. Kaplan-Meier and Cox regression analyses were performed to evaluate the effect of FDZ score on overall survival. An external cohort of 21 patients was used for validation. Results The FDZ score was significantly higher in G3 NETs compared to G3 NECs (p 0.05 group showed significantly longer survival compared to those in the FDZ≤0.05 group, with median of 34.9 vs. 12.0 months (p 0.05 (p=0.005), well differentiated disease (p=0.044), and lower Ki67 index (p=0.042) were predictors of survival. On multivariate regression, only FDZ>0.05 could independently predict longer survival with HR=0.16 (p=0.018), which was reproduced in the external validation cohort. Conclusion Combined quantification of 18F-FDG and 68Ga-DOTATATE PET/CT into a novel parameter, the FDZ score, reflects the pathologic characteristics of G3 GEP-NENs and is a prognostic indicator of overall survival independent of differentiation.

Purpose To develop a convolutional neural network (CNN)-based program to analyse maximum intensity projection (MIP) images of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) positron emission tomography (PET) scans, aimed at predicting lymph node metastasis of non-small cell lung cancer (NSCLC), and to evaluate its effectiveness in providing diagnostic assistance to radiologists.Methods We obtained PET images of NSCLC from public datasets, including those of 435 patients with available N-stage information, which were divided into a training set (n = 304) and a test set (n = 131). We generated 36 maximum intensity projection (MIP) images for each patient. A residual network (ResNet-50)-based CNN was trained using the MIP images of the training set to predict lymph node metastasis. Lymph node metastasis in the test set was predicted by the trained CNN as well as by two radiologists (R1 and R2) twice: first without and second with CNN assistance. Diagnostic performance metrics, including accuracy, were calculated, and reading times were recorded.Results In the test set, 67 (51%) patients exhibited lymph node metastases and the CNN yielded 0.748 predictive accuracy. The accuracy of the radiologists increased from 0.718 to 0.740 for R1, and from 0.679 to 0.733 for R2 with CNN assistance. The mean prediction time was significantly reduced with CNN assistance, decreasing from 11.1 to 6.9 s (p Conclusion The CNN-based program could potentially assist radiologists in predicting lymph node metastasis, increase diagnostic performance, and reduce the time for diagnosis.

A novel cystine-knot peptide–based PET radiopharmaceutical, 18F-FP-R01-MG-F2 (knottin), was developed to selectively bind to human integrin αvβ6 which is overexpressed in pancreatic cancer. The purpose of this study is to evaluate the safety, biodistribution, dosimetry, and lesion uptake of 18F-FP-R01-MG-F2 in patients with pancreatic cancer. Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUVmax) and mean SUV (SUVmean) were measured in 24 normal tissues and pancreatic cancer lesions for each patient. From the biodistribution data, the organ doses and whole-body effective dose were calculated using OLINDA/EXM software. There were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1 h post-injection, areas of high 18F-FP-R01-MG-F2 uptake included the pituitary gland, stomach, duodenum, kidneys, and bladder (average SUVmean: 9.7–14.5). Intermediate uptake was found in the normal pancreas (average SUVmean: 4.5). Mild uptake was found in the lungs and liver (average SUVmean

Purpose: To investigate the prognostic value of 18F-FDG PET/CT parameters in melanoma patients before beginning anti-PD-1 therapy. Methods: Imaging parameters including SUVmax, metabolic tumor volume (MTV), and bone marrow to liver SUVmean ratio (BLR) were measured from baseline PET/CT in 92 patients before the start of anti-PD-1 therapy. Association with survival and imaging parameters combined with clinical factors was evaluated. Clinical and laboratory data between high (> median) and low (≤ median) BLR groups were compared. Results: Multivariate analyses demonstrated that BLR was an independent prognostic factor for PFS and OS (P = 0.017, P = 0.011, respectively). The high BLR group had higher levels of white blood cell count/neutrophil count and C-Reactive Protein than the low BLR group (P < 0.05). Conclusion: Patients with high BLR were associated with poor PFS and OS, potentially explained by evidence of systemic inflammation known to be associated with immunosuppression.

To evaluate the diagnostic performance and clinical utility of 18F-fluciclovine PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). 18F-Fluciclovine scans of 165 consecutive men with BCR after primary definitive treatment with prostatectomy (n = 102) or radiotherapy (n = 63) were retrospectively evaluated. Seventy patients had concurrent imaging with at least one other conventional modality (CT (n = 31), MRI (n = 31), or bone scan (n = 26)). Findings from 18F-fluciclovine PET were compared with those from conventional imaging modalities. The positivity rate and impact of 18F-fluciclovine PET on patient management were recorded. In 33 patients who underwent at least one other PET imaging (18F-NaF PET/CT (n = 12), 68Ga-PSMA11 PET/CT (n = 5), 18F-DCFPyL PET/CT (n = 20), and 68Ga-RM2 PET/MRI (n = 5)), additional findings were evaluated. The overall positivity rate of 18F-fluciclovine PET was 67 %, which, as expected, increased with higher prostate-specific antigen (PSA) levels (ng/ml): 15 % (PSA

We investigated the ability of baseline 2-deoxy-2-[18F]fluoro-d-glucose PET/CT parameters, acquired before the start of immunotherapy, to predict development of hyperprogressive disease (HPD) in melanoma patients. We also evaluated the diagnostic performances of ratios of baseline and first restaging PET/CT parameters to diagnose HPD without information of the tumor growth kinetic ratio (TGKR) that requires pre-baseline imaging before baseline imaging (3 timepoint imaging). Seventy-six patients who underwent PET/CT before and approximately 3 months following initiation of immunotherapy were included. PET/CT parameters, including metabolic tumor volume (MTV) for all melanoma lesions and total measured tumor burden (TMTB) based on irRECIST, were measured from baseline PET/CT (MTVbase and TMTBbase) and first restaging PET/CT (MTVpost and TMTBpost). The ratios of MTV (MTVpost/MTVbase, MTVr) and TMTB (TMTBpost/TMTBbase, TMTBr) were calculated. MTVbase of HPD patients (n = 9, TGKR ≥ 2) was larger than that of non-HPD (n = 67, TGKR

False-positive bone lesions (bone pseudometastases) have been often reported in patients with esophageal cancer (EsoC). This study aimed to evaluate the vertebral 2-deoxy-2-[18F] fluoro-d-glucose (FDG) accumulation pattern in patients with newly diagnosed esophageal cancers and other malignancies (OtherT) to elucidate the possible mechanism that causes bone pseudometastasis. FDG positron emission tomography/computed tomography performed for 90 patients with EsoC, and 112 patients with OtherT was retrospectively evaluated. The uptake pattern in the thoracic (Th) and lumbar (L) vertebrae was visually assessed regarding predominance (TL, Th ≒ L; Td, Th > L; Ld, L > Th), main intensity compared with the uptake in the blood pool (BP) (Grade 1 BP), and homogeneity (homogeneous, heterogeneous, marginal, or spotty). The patterns between EsoC and OtherT and between Th and L were compared. TL, Td, and Ld patterns were observed in 51.1%, 48.9%, and 0% in EsoC and 79.7%, 20.3%, and 0% in OtherT. Though Grade 2 was most frequently observed in both groups, the ratio of Grade 3 in Th and Grade 1 in L was significantly higher in EsoC than in OtherT. Heterogeneous and spotty patterns were more frequently observed in L and in EsoC, and these were strongly associated with Td pattern. Td pattern was frequently seen, especially in EsoC, and was strongly associated with a heterogeneous or marginal pattern in the L. Heterogeneous marrow distribution with declined lumbar uptake is suspected as the mechanism of bone pseudometastasis.

F-FDG PET/CT for a 74-year-old man with elevated serum soluble interleukin 2 receptor showed multiple intense uptake in the liver, spleen, and bone. A surgical biopsy from 2 of liver tumors confirmed hepatosplenic αβ T-cell lymphoma. One and a half months after biopsy, FDG PET scan was performed again for staging before starting chemotherapy, and it showed the complete disappearance of all of the lesions. The excisional biopsy could be a possible trigger of his spontaneous regression.

To show that augmented reality (AR) visualization of single-photon emission computed tomography (SPECT)/computed tomography (CT) data in 3D can be used to accurately localize targets in the head and neck region.Eight head and neck styrofoam phantoms were painted with a mixture of radioactive solution (Tc-99m) detectable with a handheld gamma probe and fluorescent ink visible only under ultraviolet (UV) light to create 10-20 simulated lymph nodes on their surface. After obtaining SPECT/CT images of these phantoms, virtual renderings of the nodes were generated from the SPECT/CT data and displayed using a commercially available AR headset. For each of three physician evaluators, the time required to localize lymph node targets was recorded (1) using the gamma probe alone and (2) using the gamma probe while wearing the AR headset. In addition, the surface localization accuracy when using the AR headset was evaluated by measuring the misalignment between the locations visually marked by the evaluators and the ground truth locations identified using UV stimulation of the ink at the site of the nodes.For all three evaluators, using the AR headset significantly reduced the time to detect targets (P = 0.012, respectively) compared to using the gamma probe alone. The average misalignment between the location marked by the evaluators and the ground truth location was 8.6 mm.AR visualization of SPECT/CT data in 3D allows for accurate localization of targets in the head and neck region, and may reduce the localization time of targets.

A novel cystine-knot peptide-based PET radiopharmaceutical,Fifteen patients (6 men, 9 women) with histologically confirmed pancreatic cancer were prospectively enrolled and underwent knottin PET/CT between March 2017 and February 2021 (ClinicalTrials.gov Identifier NCT02683824). Vital signs and laboratory results were collected before and after the imaging scans. Maximum standardized uptake values (SUVThere were no significant changes in vital signs or laboratory values that qualified as adverse events or serious adverse events. At 1 h post-injection, areas of highNCT02683824.

High-grade gastroenteropancreatic neuroendocrine neoplasms (G3 GEP-NENs) are pathologically classified into well differentiated neuroendocrine tumors (G3 NETs) and poorly differentiated neuroendocrine carcinomas (G3 NECs). Using a novel parameter, we examined the prognostic value ofA total of 31 patients with G3 GEP-NENs were reviewed. For each patient, the SUVmax onThe FDZ score was significantly higher in G3 NETs compared to G3 NECs (p0.001), and was inversely correlated with Ki67 index (RCombined quantification of

A mobile positron emission tomography (PET) scanner called flexible PET (fxPET), designed to fit existing magnetic resonance imaging (MRI) or computed tomography (CT) system, has been developed. The purpose of this study was to evaluate the image quality, lesion detection rate, and quantitative values of fxPET compared with conventional bismuth germanium oxide (BGO)-based PET/CT without time-of-flight capability. Fifty-nine patients underwent whole-body (WB) PET/CT scans approximately 1 h after injection of 2-deoxy-2-[18F]fluoro-D-glucose, followed by the fxPET scans with detectors located above and below the patients (layout A) and with detectors closer to the patients (layout B). Two readers assessed the image quality using a 4-point grade for each layout and reached a consensus. We evaluated the differences and/or correlations between fxPET and WB PET/CT, including the lesion detection rates, the standardized uptake value (SUV), the metabolic tumor volume (MTV), the total lesion glycolysis (TLG), the tumor-to-normal liver ratio (TLR), and the background liver signal-to-noise ratio (SNR). The image quality of layout B was better than layout A (p

OBJECTIVES We investigated clinical characteristics of patients with extremely increased or decreased physiologic F-FDG uptake of the liver and their prognosis. METHODS One thousand four hundred eighty-seven PET/CT scans of patients with known or suspected malignancy were retrospectively analyzed. A spherical volume of interest (3 cm in diameter) was set on the right lobe of the liver to calculate the SUVmean. Scans with extremely high (SUVmean >97.5th percentile) and low (SUVmean

Purpose of the report False-positive bone lesions mimicking bone metastases (bone pseudometastasis) on F-FDG PET/CT have often been reported in patients with esophageal cancer. We aimed to evaluate the prevalence and features of these lesions in Japanese patients with esophageal cancer. Methods In this retrospective study, we analyzed 83 FDG PET/CT studies for initial staging of esophageal cancer, and extracted patients with 1 or more localized high uptake sites with no subsequent progression, which were therefore judged to be bone pseudometastasis. The FDG PET/CT imaging features of the bone pseudometastasis were evaluated, and other available imaging and clinical features reviewed. Results Of the 83 patients, 7 had bone pseudometastasis. All 7 were males diagnosed with squamous cell cancer, of which 5 had T1a tumors. Bone pseudometastasis showed normal or ill-defined hyperdense (nonosteolytic) sites compared with the surrounding area on the CT. Additionally, accumulation in the upper vertebral levels of each case was contiguously high compared with the lumbar spines (we named this finding "contiguous accumulation"). On MRI, these findings were visualized as low signals on T1-weighted imaging (T1WI) and T2WI images but were unclear on fat-suppressed T2WI images. Conclusions Among all PET/CT performed for staging of esophageal cancer, 8.3% demonstrated bone pseudometastasis characterized by heterogeneous distribution with severe fatty degeneration of bone marrow accompanied by contiguous accumulation. Caution is required during diagnoses of bone lesions in esophageal cancer patients in Japan to prevent inappropriate therapeutic choices.

[Purpose]To evaluate the clinical feasibility of a newly developed mobile PET system with MR-compatibility (flexible PET; fxPET), compared with conventional PET (cPET)/CT for brain imaging.[Methods]Twenty-one patients underwent cPET/CT with subsequent fxPET/MRI using 18F-FDG. As qualitative evaluation, we visually rated image quality of MR and PET images using a four-point scoring system. We evaluated overall image quality for MR, while we evaluated overall image quality, sharpness and lesion contrast. As quantitative evaluation, we compared registration accuracy between two modalities [(fxPET and MRI) and (cPET and CT)] measuring spatial coordinates. We also examined the accuracy of regional 18F-FDG uptake.[Results]All acquired images were of diagnostic quality and the number of detected lesions did not differ significantly between fxPET/MR and cPET/CT. Mean misregistration was significantly larger with fxPET/MRI than with cPET/CT. SUVmax and SUVmean for fxPET and cPET showed high correlations in the lesions (R = 0.84, 0.79; P

To evaluate the diagnostic performance and clinical utility ofThe overall positivity rate of

Our purpose was to investigate the prognostic value of

We investigated the ability of baseline 2-deoxy-2-[Seventy-six patients who underwent PET/CT before and approximately 3 months following initiation of immunotherapy were included. PET/CT parameters, including metabolic tumor volume (MTV) for all melanoma lesions and total measured tumor burden (TMTB) based on irRECIST, were measured from baseline PET/CT (MTVMTVPatients at high risk of developing HPD could not be accurately identified based on baseline PET/CT parameters. The ratios of baseline and first restaging PET/CT parameters may be helpful to diagnose HPD, when patients do not undergo pre-baseline imaging.

The purpose of this study was to investigate the prognostic value of whole-body metabolic tumor volume (MTV) and other metabolic tumor parameters, obtained from baseline and first restaging 18F-FDG PET/CT scans in melanoma patients treated with immune checkpoint inhibitors (ICIs). Eighty-five consecutive melanoma patients (M, 57; F, 28) treated with ICIs who underwent PET/CT scans before and approximately 3 months after the start of immunotherapy were retrospectively enrolled. Metabolic tumor parameters including MTV for all melanoma lesions were measured on each scan. A Cox proportional hazards model was used for univariate and multivariate analyses of metabolic parameters combined with known clinical prognostic factors associated with overall survival (OS). Kaplan–Meier curves for patients dichotomized based on median values of imaging parameters were generated. The median OS time in all patients was 45 months (95% CI 24–45 months). Univariate analysis demonstrated that MTV obtained from first restaging PET/CT scans (MTVpost) was the strongest prognostic factor for OS among PET/CT parameters (P

Effect of CD47 Blockade on Vascular Inflammation Patients in a trial of the anti-CD47 antibody magrolimab for treatment of lymphoma underwent 18F-FDG PET–CT. Treatment was found to reduce arterial ...

We report a case of anti-N-methyl-D-aspartate-receptor (anti-NMDAR) encephalitis associated with an immature teratoma developed in a 38-year-old woman. Positron emission tomography (PET) revealed focal intense uptake of F-fluorodeoxyglucose in an area of the brain corresponding to the right medial temporal lobe as well as an intrapelvic tumor. After the PET examination, the patient complained of disorientation and short-term memory loss. The ovarian tumor was resected and diagnosed as an immature teratoma. The cerebrospinal fluid analysis was positive for anti-NMDAR antibody. After surgery, the patient's neurologic symptoms improved. The PET finding of encephalitis associated with an immature teratoma was unexpected.

This retrospective study compared the diagnostic performances of quantitative versus visual analyses of I-MIBG scintigraphy in patients with suspected pheochromocytoma and paraganglioma (PPGL).SPECT images were obtained 6 and/or 24 h after MIBG injection from 68 patients with clinically suspected PPGL, with attenuation correction by low-dose unenhanced CT. Planar images were also obtained at each time point. SUVs of retroperitoneal tumors, including PPGLs, and physiological uptake by normal organs were measured using the SPECT images. The diagnostic performance of the quantitative assessment in differentiating PPGLs from other lesions or normal adrenal glands was assessed using receiver operating characteristic analysis. The planar scans and 6-h and 24-h SPECT/CT images were also assessed visually.PPGLs showed a significantly higher SUVmax (mean ± SD = 9.97 ± 3.86) than other retroperitoneal lesions (3.85 ± 1.51) or normal adrenal glands (3.91 ± 1.20). At an optimal cut-off of 6.57, the sensitivity, specificity, and accuracy of the quantitative assessment for 6-h SPECT/CT in differentiating PPGLs was 78.6%, 96.3%, and 92.6%, respectively; the area under the curve was 0.878. The diagnostic performance did not significantly differ between the quantitative and visual analyses, but the specificity of the former tended to be higher at 6 h (96.3% vs. 90.7%) and at 24 h (91.2% vs. 82.4%).The specificity, but not the sensitivity, of the quantitative approach was higher than that of visual assessment in differentiating PPGLs from other retroperitoneal pathologies and from physiological uptake in the normal adrenal gland.

We report a case of splenic marginal zone B-cell lymphoma discovered in a 73-year-old man with cold agglutinin disease. PET/CT revealed splenomegaly with focally intense uptake of F-FDG and diffusely increased bone marrow uptake, which was considered to be secondary to hemolytic anemia. Splenectomy was performed. The histopathology of the spleen showed splenic marginal zone B-cell lymphoma with partial splenic infarction, which correlated with the area of focal intense FDG uptake. Depending on the time since onset, splenic infarctions can present as focal FDG accumulation.

The current study tested a newly developed flexible PET (fxPET) scanner prototype. This fxPET system involves dual arc-shaped detectors based on silicon photomultipliers that are designed to fit existing MRI devices, allowing us to obtain fused PET and MR images by sequential PET and MR scanning. This prospective study sought to evaluate the image quality, lesion detection rate, and quantitative values of fxPET in comparison with conventional whole-body (WB) PET and to assess the accuracy of registration. Methods: Seventeen patients with suspected or known malignant tumors were analyzed. Approximately 1 h after intravenous injection of 18F-FDG, WB PET/CT was performed, followed by fxPET and MRI. For reconstruction of fxPET images, MRI-based attenuation correction was applied. The quality of fxPET images was visually assessed, and the number of detected lesions was compared between the 2 imaging methods. SUVmax and maximum average SUV within a 1 cm3 spheric volume (SUVpeak) of lesions were also compared. In addition, the magnitude of misregistration between fxPET and MR images was evaluated. Results: The image quality of fxPET was acceptable for diagnosis of malignant tumors. There was no significant difference in detectability of malignant lesions between fxPET and WB PET (P > 0.05). However, the fxPET system did not exhibit superior performance to the WB PET system. There were strong positive correlations between the 2 imaging modalities in SUVmax (ρ = 0.88) and SUVpeak (ρ = 0.81). SUVmax and SUVpeak measured with fxPET were approximately 1.1-fold greater than measured with WB PET. The average misregistration between fxPET and MR images was 5.5 ± 3.4 mm. Conclusion: Our preliminary data indicate that running an fxPET scanner near an existing MRI system provides visually and quantitatively acceptable fused PET/MR images for diagnosis of malignant lesions.

This article was updated to correct the “greater than or equal to” (≥) symbols in Tables 4 and 5, which incorrectly appeared as “greater than” (>) symbols.

目的：微小気泡を用いた低侵襲治療法として，超音波照射による温熱効果及び非温熱効果を利用した手法が開発検討されているが，微小気泡は生体内では血流と共に拡散するため，これまでは血流に任せる以外に送達手段が無く，投入効率と副作用の問題があった．対象と方法：本論文では微小気泡の動態を制御するため，複数の超音波音源と単純な形状の分岐を有する模擬血管を用いて，微小気泡の流路選択性能を向上させる方法について検討した．超音波が微小気泡に及ぼす作用力には，伝搬方向への推進力となるprimary Bjerknes forceと，気泡同士が結合した凝集体を形成する引力となるsecondary Bjerknes forceがあるが，前者では流路の分岐形状に対する音波照射角度等の，後者では凝集体のサイズとその飽和時間に必要な音波のパラメータをそれぞれ導出した．これらの両方を同一空間に発生させ，凝集体の形成後に目的の経路に誘導する実験を行った．結果：凝集体を形成しない場合に比べて，凝集体を押し出した場合の誘導率が1.3‐5.5倍向上することを確認した．凝集体の非形成時には中心周波数5 MHzの音波が最も推進力が得られた一方，凝集体形成時には中心周波数が2 MHzで誘導率が最も高くなることを確認した．結論：以上のことより，凝集体自体が一個の微小気泡であると見なした場合のサイズから導出される共振周波数に近いことが推測された．

We have previously reported our attempts to control microbubbles (microcapsules) behavior in flow by primary Bjerknes force to increase the local concentration of the bubbles at a diseased part. However, there was a limitation in efficiency to propel bubbles of μm-order size. Thus we consider that forming aggregates of bubbles is effective to be propelled before entering into an ultrasound field by making use of secondary Bjerknes force under continuous ultrasound exposure. In this study, we observed the phenomena of aggregates formation by confirming variation of diameter and density of aggregates under various conditions of ultrasound exposure. Then we elucidated frequency dependence of the size of aggregates of micro-bubbles.

We have proposed a physical DDS (Drug Delivery System) which makes use of microcapsules of μm size, which may contain a specified drug and also are easily affected by ultrasound exposure near their resonant frequency, to release various kinds of medications. These capsules are easily detected and actuated by ultrasound. However, because of the diffusion of capsules after injection into human body, it was difficult to enhance the efficiency of drug delivery. Thus we have considered a method for controlling the density of capsules in flow which uses acoustic radiation force, which moves the capsules to balance flow resistance. We have experimented with trapping microcapsules or microbubbles in flow of an artificial blood vessel. We have evaluated the effect of radiation force by measuring the trapped area of capsules or bubbles for various frequencies, sound pressures, and exposure times of sinusoidal ultrasound. The trapped area of capsules or bubbles increased with sound pressure and exposure time, and decreased with frequency. From those results, we have derived optimal conditions for trapping the capsules or bubbles.

We have already reported our attempt to constrain direction of microcapsules in flow owing to an acoustic radiation force. However, the diameter of capsules was too large not to be applied in vivo. Furthermore, acoustic radiation force affected only in focal area because focused ultrasound was used. Thus we have improved our experiment by using microcapsules as small as blood cells and introducing a plane wave of ultrasound. We prepared an artificial blood vessel including a Y-form bifurcation established two observation areas. Then we newly defined the induction index to evaluate the difference of capsule density in two paths of downstream. As the result, optimum angle of ultrasound emission to induce to desired path was derived. And the induction index increased in proportion to the central frequency of ultrasound, which is affected by forming aggregation of capsules to receive more radiation force.

Micrometer-sized microcapsules collapse upon exposure to ultrasound. Use of this phenomenon for a drug delivery system (DDS), not only for local delivery of medication but also for gene therapy, should be possible. However, enhancing the efficiency of medication is limited because capsules in suspension diffuse in the human body after injection, since the motion of capsules in blood flow cannot be controlled. To control the behavior of microcapsules, acoustic radiation force was introduced. We detected local changes in microcapsule density by producing acoustic radiation force in an artificial blood vessel. Furthermore, we theoretically estimated the conditions required for active path selection of capsules at a bifurcation point in the artificial blood vessel. We observed the difference in capsule density at both in the bifurcation point and in alternative paths downstream of the bifurcation point for different the acoustic radiation forces. Also we confirmed the microcapsules are trapped against flow with the condition when the acoustic radiation force is more than fluid resistance of the capsules. The possibility of controlling capsule flow towards a specific point in a blood vessel was demonstrated.

Microcapsules of μm order collapse themselves after ultrasound emission. Applying this technique as drug delivery system (DDS), not only local medication but also gene therapy method should be possible. However, it has been limitation to enhance the efficiency of medication because capsules suspension spreads in human body after the injection, where motion of capsules in blood flow cannot be controlled. To affect behavior of microcapsules, acoustic radiation force was introduced. We have observed the local aggregation of microcapsules by producing local acoustic radiation force in the artificial blood vessel. Then we estimated amount of trapped capsules by optical image processing. We confirmed fluid microcapsules of similar diameter with red blood cell were trapped in the middle of the path and by ultrasound of sinusoidal signal of 1 MHz. The condition to trap capsules was indicated by higher sound pressure and lower flow velocity.

Microcapsules of µm order collapse themselves after ultrasound emission. Recently, this technique attracts attention to apply to the gene delivery because virus vector is not necessary. However, it has been limitation to enhance the efficiency of medication because capsules suspension diffuses after the injection, where motion of capsules in blood flow cannot be controlled. To affect behavior of microcapsules, acoustic radiation force was introduced. Then we have detected the local change of microcapsules density by producing acoustic radiation force in the artificial blood vessel. Furthermore, we estimated theoretically condition for active path selection of capsules at the bifurcation in the artificial blood vessel. We observed the difference of density in capsules according to the acoustic radiation force and the produced point. Comparing the experimental results with theoretical equations, the condition for active path selection is calculated from acoustic radiation force and fluid resistance of capsules. It showed a possibility to control capsules direction and to lead to an objective point in blood vessel.

We have proposed a method to control microbubbles by making use of acoustic radiation force, which is generated with acoustic propagation, to correspond to therapeutic applications of ultrasound. By preventing bubbles from passing through the desired target area, the local concentration of bubbles can be enhanced. However, we have never experimentally confirmed this phenomenon under in vivo conditions or close to those. Thus, we carried out an experiment to evaluate the trapping performance of bubbles using a suspension of red blood cells (RBCs) and an artificial blood vessel. By defining the trapping index to evaluate the amount of trapped microbubbles, we have confirmed that the trapping performance was enhanced according to the concentration of RBCs and the sound pressure, but not according to the central frequency of ultrasound. The results indicate that the existence of RBCs near microbubbles contributed to the increase in the size of aggregations propelled against the vessel wall.

We have ever reported our attempt to control the direction of microcapsules in flow by acoustic radiation force. However, the diameter of capsules was too large to be applied in vivo. Furthermore, the acoustic radiation force affected only the focal area because focused ultrasound was used. Thus, we have improved our experiment by using microcapsules as small as blood cells and introducing a plane wave of ultrasound. We prepared an artificial blood vessel including a Y-form bifurcation established in two observation areas. Then, we newly defined the induction index to evaluate the difference in capsule density in two downstream paths. As a result, the optimum angle of ultrasound emission to induct to the desired path was derived. The induction index increased in proportion to the central frequency of ultrasound, which is affected by the aggregation of capsules to receive more acoustic radiation force.

Micrometer-sized microcapsules collapse upon exposure to ultrasound. Use of this phenomenon for a drug delivery system (DDS), not only for local delivery of medication but also for gene therapy, should be possible. However, enhancing the efficiency of medication is limited because capsules in suspension diffuse in the human body after injection, since the motion of capsules in blood flow cannot be controlled. To control the behavior of microcapsules, acoustic radiation force was introduced. We detected local changes in microcapsule density by producing acoustic radiation force in an artificial blood vessel. Furthermore, we theoretically estimated the conditions required for active path selection of capsules at a bifurcation point in the artificial blood vessel. We observed the difference in capsule density at both in the bifurcation point and in alternative paths downstream of the bifurcation point for different acoustic radiation forces. Comparing the experimental results with those obtained theoretically, the conditions for active path selection were calculated from the acoustic radiation force and fluid resistance of the capsules. The possibility of controlling capsule flow towards a specific point in a blood vessel was demonstrated.