Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast ca...Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.展开更多
BACKGROUND Radionuclides produce Cherenkov radiation(CR),which can potentially activate photosensitizers(PSs)in phototherapy.Several groups have studied Cherenkov energy transfer to PSs using optical imaging;however,c...BACKGROUND Radionuclides produce Cherenkov radiation(CR),which can potentially activate photosensitizers(PSs)in phototherapy.Several groups have studied Cherenkov energy transfer to PSs using optical imaging;however,cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge.Many laboratories face the need for expensive dedicated equipment.AIM To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs.METHODS The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs.To mitigate the need for expensive dedicated equipment and achieve the aim of the study,we developed a method that utilizes a chargecoupled device optical imaging system and appropriate long-pass filters of different wavelengths(manual sequential application of long-pass filters of 515,580,645,700,750,and 800 nm).Tetrakis(4-carboxyphenyl)porphyrin(TCPP)was utilized as a model PS.Different doses of copper-64(^(64)CuCl_(2))(4,2,and 1 mCi)were used as CR-producing radionuclides.Imaging and data acquisition were performed 0.5 h after sample preparation.Differential image analysis was conducted by using ImageJ software(National Institutes of Health)to visually evaluate TCPP fluorescence.RESULTS The maximum absorbance of TCPP was at 390-430 nm,and the emission peak was at 670 nm.The CR and CRinduced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above.The emission spectra of TCPP with a peak in the 645-700 nm window were obtained by calculation and subtraction based on the serial signal intensity(total flux)difference between^(64)CuCl_(2)+TCPP and^(64)CuCl_(2).Moreover,the differential fluorescence images of TCPP were obtained by subtracting the^(64)CuCl_(2)image from the^(64)CuCl_(2)+TCPP image.The experimental results considering different^(64)CuCl_(2)doses showed a dosedependent trend.These results demonstrate that a bioluminescence imaging device coupled with different longpass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP.CONCLUSION This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.展开更多
Background A medical content-based image retrieval(CBIR)system is designed to retrieve images from large imaging repositories that are visually similar to a user′s query image.CBIR is widely used in evidence-based di...Background A medical content-based image retrieval(CBIR)system is designed to retrieve images from large imaging repositories that are visually similar to a user′s query image.CBIR is widely used in evidence-based diagnosis,teaching,and research.Although the retrieval accuracy has largely improved,there has been limited development toward visualizing important image features that indicate the similarity of retrieved images.Despite the prevalence of 3D volumetric data in medical imaging such as computed tomography(CT),current CBIR systems still rely on 2D cross-sectional views for the visualization of retrieved images.Such 2D visualization requires users to browse through the image stacks to confirm the similarity of the retrieved images and often involves mental reconstruction of 3D information,including the size,shape,and spatial relations of multiple structures.This process is time-consuming and reliant on users'experience.Methods In this study,we proposed an importance-aware 3D volume visualization method.The rendering parameters were automatically optimized to maximize the visibility of important structures that were detected and prioritized in the retrieval process.We then integrated the proposed visualization into a CBIR system,thereby complementing the 2D cross-sectional views for relevance feedback and further analyses.Results Our preliminary results demonstrate that 3D visualization can provide additional information using multimodal positron emission tomography and computed tomography(PETCT)images of a non-small cell lung cancer dataset.展开更多
AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(...AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.展开更多
Many studies demonstrate that conventional anticancer drugs elevate intracellular level of reactive oxygen species(ROS) and alter redox-homeostasis of cancer cells. It is widely accepted that anticancer effect of thes...Many studies demonstrate that conventional anticancer drugs elevate intracellular level of reactive oxygen species(ROS) and alter redox-homeostasis of cancer cells. It is widely accepted that anticancer effect of these chemotherapeutics is due to induction of oxidative stress and ROS-mediated apoptosis in cancer. On the other hand, the harmful side effects of conventional anticancer chemotherapy are also due to increased production of ROS and disruption of redox-homeostasis of normal cells and tissues. This article describes the mechanisms for triggering and modulation of apoptosis through ROS-dependent and ROS-independent pathways. We try to answer the question: "Is it possible to induce highly specific apoptosis only in cancer cells, without overproduction of ROS, as well as without harmful effects on normal cells and tissues?" The review also suggests a new therapeutic strategy for selective killing of cancer cells, without significant impact on viability of normal cells and tissues, by combining anticancer drugs with redox-modulators, affecting specific signaling pathways and avoiding oxidative stress.展开更多
AIM To compare ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma.METHODS Patients with newly diagnosed gastric lymphoma or...AIM To compare ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma.METHODS Patients with newly diagnosed gastric lymphoma or gastric carcinoma who underwent ^(18)F-FDG PET/CT prior to treatment were included in this study. We reviewed and analyzed the PET/CT features of gastric wall lesions,including FDG avidity,pattern(focal/diffuse),and intensity [maximal standard uptake value:(SUVmax)]. The correlation of SUVmax with gastricclinicopathological variables was investigated by χ~2 test,and receiver-operating characteristic(ROC) curve analysis was performed to determine the differential diagnostic value of SUVmax-associated parameters in gastric lymphoma and gastric carcinoma. RESULTS Fifty-two patients with gastric lymphoma and 73 with gastric carcinoma were included in this study. Abnormal gastric FDG accumulation was found in 49 patients(94.23%) with gastric lymphoma and 65 patients(89.04%) with gastric carcinoma. Gastric lymphoma patients predominantly presented with type Ⅰ and type Ⅱ lesions,whereas gastric carcinoma patients mainly had type Ⅲ lesions. The SUVmax(13.39 ± 9.24 vs 8.35 ± 5.80,P < 0.001) and SUVmax/THKmax(maximal thickness)(7.96 ± 4.02 vs 4.88 ± 3.32,P < 0.001) were both higher in patients with gastric lymphoma compared with gastric carcinoma. ROC curve analysis suggested a better performance of SUVmax/THKmax in the evaluation of gastric lesions between gastric lymphoma and gastric carcinoma in comparison with that of SUVmax alone.CONCLUSION PET/CT features differ between gastric lymphoma and carcinoma,which can improve PET/CT evaluation of gastric wall lesions and help differentiate gastric lymphoma from gastric carcinoma.展开更多
Objective:A high rate of unnecessary thymectomies has been reported.This study aimed to distinguish primary mediastinal lymphomas(PMLs)from thymic epithelial tumors(TETs)by evaluating volumetric and metabolic paramete...Objective:A high rate of unnecessary thymectomies has been reported.This study aimed to distinguish primary mediastinal lymphomas(PMLs)from thymic epithelial tumors(TETs)by evaluating volumetric and metabolic parameters with l8F-FDG PET/CT.Methods:A total of 136 patients who were pathologically diagnosed with TETs or PMLs were enrolled,and 18F-FDG PET/CT was performed before therapy.Volumetric parameters,including the mean SUV(SUVmean),metabolic tumor volume(MTV),total lesion glycolysis(TLG),and SUVmax,were determined and compared between the 2 subtypes.The diagnostic performance of these parameters was evaluated with receiver operating characteristic(ROC)curve analysis.Results:All parameters significantly differed between patients with PMLs and TETs.Patients with lymphomas were younger and had higher SUVmean,SUVmax,TLG,and MTV values than patients with TETs.The MTV and TLG values had similar diagnostic performance.ROC analysis indicated that the areas under the curves of the SUVmean and SUVmax values performed similarly(approximately 0.76)in differentiating patients with PMLs from TETs,and both values were better than the MTV and TLG values.When age was included with the SUVmax in differentiating TETs from PMLs,the AUC was 0.91,and the sensitivity and specificity increased to 80%and 93%,respectively.Conclusions:The SUVmax and volumetric parameters of 18F-FDG PET/CT can be used to distinguish patients with PMLs versus TETs,and thus may aid in preventing unnecessary thymectomies or other invasive operations.展开更多
AIM:To present our initial experience with computed tomography guided radiofrequency ablation(RFA) of osteoid osteoma(OO) in our institution.METHODS:RFA was performed on eight patients(5 males and 3 females) with clin...AIM:To present our initial experience with computed tomography guided radiofrequency ablation(RFA) of osteoid osteoma(OO) in our institution.METHODS:RFA was performed on eight patients(5 males and 3 females) with clinically and radiologically diagnosed OO(femoral neck,n = 4;femoral diaphysis,n = 2;tibial diaphysis,n = 1;fibular diaphysis,n = 1).Ablation was performed using an electrode with a 10-mm exposed tip for a total of 4-6 min at a targeted temperature of 90 degrees Celsius.No cooling system was used.The intervention was accepted as technically successful if the tip of the electrode could be placed within the center of the nidus.We defined clinical success as a disappearance within 2 wk after treatment of symptoms that had manifested at presentation.RESULTS:All procedures were technically successful.No major or immediate complications were observed.Clinical success was achieved in six of eight patients in the first procedure.A second procedure was performed for two patients who had recurrent or continued pain,and one of these cases was successfully treated.The overall rate of success was 87.5%(7/8).No complication was observed.CONCLUSION:Our preliminary results indicate a favorable success rate and no complications and are compatible with the previous reports of RFA of OO.展开更多
AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer model.METHODS Phosphorylation of Akt, m TOR, the downstrea...AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer model.METHODS Phosphorylation of Akt, m TOR, the downstream effectors eukaryotic initiation factor 4 E binding protein 1(4 EBP1) and S6 ribosomal protein(S6) were evaluated in Bx PC-3 human pancreatic cancer cells treated with Yttrium-^(90)(^(90) Y) labeled anti-integrin α6β4 antibody(ITGA6 B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay. Therapeutic efficacy enhancement by oral BEZ235 administration was assessed using mice bearing Bx PC-3 xenograft tumors. Tumor volume measurements and immunohistochemical analyses(cell proliferation marker Ki-67, DNA damage marker p-H2 AX and p-4 EBP1 staining) of tumors were performed for evaluation of combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235, or each arm alone.RESULTS We found that phosphorylation of Akt(p-Akt), 4 EBP1(p-4 EBP1) and S6(p-S6) was inhibited by BEZ235. Colony formation in Bx PC-3 cells was additively suppressed by the combination of ^(90) Y-ITGA6 B4 and BEZ235. Pretreatment with BEZ235 before ^(90) Y-ITGA6 B4 exposure resulted in significant reduction of cells plating efficiency(PE)(0.54 ± 0.11 vs 2.81 ± 0.14 with 185 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01; 0.39 ± 0.08 vs 1.88 ± 0.09 with 370 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01) when 5 × 10~3 cells per dish were plated. In vivo, the combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235 enhanced the inhibition of tumor growth and statistically significant differences of relative tumor volume were observed for 27 d after the treatment start date when compared with the ^(90) Y-ITGA6 B4 single injection treatment(1.03 ± 0.38 vs 1.5 ± 0.15 at Day 27, P < 0.05), and for 41 d when compared with the BEZ235 treatment alone(1.8 ± 0.7 vs 3.14 ± 1.19 at Day 41, P < 0.05). Tumors from treatment groups showed reduction in volumes, decreased Ki-67-positive cells, increased p-H2 AX-positive cells and decreased p-4 EBP1 expression. CONCLUSION The therapeutic efficacy of ^(90) Y-ITGA6 B4-RIT can be improved by combining with dual PI3 K and m TOR inhibitor, BEZ235, in a pancreatic cancer model suggesting potential clinical application.展开更多
Extragonadal primary yolk sac tumor of the intestinal tract origin is exceedingly rare. Through a multiple disciplinary team, the diagnosis and treatment of primary intestinal yolk sac tumor were further defined. We r...Extragonadal primary yolk sac tumor of the intestinal tract origin is exceedingly rare. Through a multiple disciplinary team, the diagnosis and treatment of primary intestinal yolk sac tumor were further defined. We report 2 such cases with detailed histologic and immunohistochemical analysis. The two patients were a 7-year-old girl and a 29-year-old woman. Both of them preoperatively had an elevated serum alpha fetoprotein(AFP) level(≥ 1,210 ng/mL). The tumors are located in the intestine and imaging examination indicated the rectum as the primary site. Grossly the mass was grey-white and crisp texture. Microscopic examination featured reticular, microcystic, macrocystic, papillary, solid, and some glandular patterns. Immunohistochemically,tumor cells of both cases were positive for SALL4, AFP, pan-cytokeratin(AE1/AE3), and glypican-3. Simultaneously, a stain for EMA, OCT4, CD30, HCG, vimentin and CK20 were negative in all 2 neoplasms. The features of morphology,immunohistochemistry, laboratory examinations and imaging studies consist of the diagnosis of primary yolk sac tumor of the intestine.展开更多
Objective: Computed tomography (CT)-based attenuation correction (CTAC) offers the clear benefit of reliable reconstruction of single-photon emission computed tomography (SPECT) images through its ability to achieve o...Objective: Computed tomography (CT)-based attenuation correction (CTAC) offers the clear benefit of reliable reconstruction of single-photon emission computed tomography (SPECT) images through its ability to achieve object-specific attenuation maps, but artifacts from dense materials often deteriorate CTAC performance. Therefore, we investigate the feasibility of CTAC in the presence of dense materials using dual-energy virtual monochromatic CT data. Methods: A sodium pertechnetate-filled cylindrical uniform phantom, with a pair of undiluted iodine syringes attached, is scanned with a dual-source CT scanner to obtain both single-energy (120 kVp) polychromatic and dual-energy (80 kVp/140 kVp with tin filtering) virtual monochromatic CT images. The single-energy and the dual-energy CT images are then converted to attenuation maps at 141 keV. SPECT images are reconstructed from 99mTc emission data of the phantom using each single-energy and dual-energy attenuation map and incorporating CTAC procedure. A region-of-in- terest analysis is performed to quantitatively compare the attenuation maps between the single-energy and the dual-energy techniques, each at an iodine-free position and a position adjacent to the iodine solutions. Results: At the iodine-free position, the phantom provides a uniform distribution of attenuation maps in both the single-energy and the dual-energy techniques. In the presence of adjacent iodine solutions, however, severe artifacts appeare in the single-energy CT images. These artifacts make attenuation values fluctuate, resulting in erroneous pixel values in the CTAC SPECT images. In contrast, dual-energy CT strongly suppresses the artifacts and hence improves the uniformity of the attenuation maps and the resultant SPECT images. Conclusions: Dual-energy CT with virtual monochromatic reconstruction has the potential to substantially reduce artifacts arising from dense materials. It has the potential to improve the accuracy of attenuation maps and the resultant CTAC SPECT images.展开更多
BACKGROUND Photodynamic therapy(PDT)is a minimally invasive form of cancer therapy,and the development of a novel photosensitizer(PS)with optimal properties is important for enhancing PDT efficacy.Folate receptor(FR)m...BACKGROUND Photodynamic therapy(PDT)is a minimally invasive form of cancer therapy,and the development of a novel photosensitizer(PS)with optimal properties is important for enhancing PDT efficacy.Folate receptor(FR)membrane protein is frequently overexpressed in 40%of human cancer and a good candidate for tumor-specific targeting.Specific active targeting of PS to FR can be achieved by conjugation with the folate moiety.A folate-linked,near-infrared(NIR)-sensitive probe,folate-Si-rhodamine-1(FolateSiR-1),was previously developed and is expected to be applicable to NIR-PDT.AIM To investigate the therapeutic efficacy of NIR-PDT induced by FolateSiR-1,a FRtargeted PS,in preclinical cancer models.METHODS FolateSiR-1 was developed by conjugating a folate moiety to the Si-rhodamine derivative through a negatively charged tripeptide linker.FR expression in the designated cell lines was examined by western blotting(WB).The selective binding of FolateSiR-1 to FR was confirmed in FR overexpressing KB cells(FR+)and tumors by fluorescence microscopy and in vivo fluorescence imaging.Low FR expressing OVCAR-3 and A4 cell lines were used as negative controls(FR-).The NIR light(635±3 nm)-induced phototoxic effect of FolateSiR-1 was evaluated by cell viability imaging assays.The time-dependent distribution of FolateSiR-1 and its specific accumulation in KB tumors was determined using in vivo longitudinal fluorescence imaging.The PDT effect of FolateSiR-1 was evaluated in KB tumor bearing mice divided into four experimental groups:(1)FolateSiR-1(100μmol/L)alone;(2)FolateSiR-1(100μmol/L)followed by NIR irradiation(50 J/cm2);(3)NIR irradiation(50 J/cm2)alone;and(4)no treatment.Tumor volume measurement and immunohistochemical(IHC)and histological examinations of the tumors were performed to analyze the effect of PDT.RESULTS High FR expression was observed in the KB cells by WB,but not in the OVCAR-3 and A4 cells.Substantial FR-specific binding of FolateSiR-1 was observed by in vitro and in vivo fluorescence imaging.Cell viability imaging assays showed that NIR-PDT induced cell death in KB cells.In vivo longitudinal fluorescence imaging showed rapid peak accumulation of FolateSiR-1 in the KB tumors 2 h after injection.In vivo PDT conducted at this time point caused tumor growth delay.The relative tumor volumes in the PDT group were significantly reduced compared to those in the other groups[5.81±1.74(NIR-PDT)vs 12.24±2.48(Folate-SiR-1),vs 11.84±3.67(IR),vs 12.98±2.78(Untreated),at Day 16,P<0.05].IHC analysis revealed reduced proliferation marker Ki-67-positive cells in the PDT treated tumors,and hematoxylin-eosin staining revealed features of necrotic-and apoptotic cell death.CONCLUSION FolateSiR-1 has potential for use in PDT,and FR-targeted NIR-PDT may open a new effective strategy for the treatment of FR-overexpressing tumors.展开更多
Paradoxical reduction of cerebral blood flow(CBF)after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen ex...Paradoxical reduction of cerebral blood flow(CBF)after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction(OEF).In this study,we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume(CBV)as a marker of regional cerebral perfusion pressure(CPP).In 37patients with unilateral internal carotid or middle cerebral arterial(MCA)steno-occlusive disease and8 normal controls,the baseline CBF(CBF_b),CBV,OEF,cerebral oxygen metabolic rate(CMRO_2),and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by^(15)O positron emission tomography.Paradoxical CBF_b reduction was found in 28 of 74 regions(18of 37 patients)in the ipsilateral hemisphere.High CBF_b(>47.6 mL/100 mL/min,n=7)was associated with normal CBF_b/CBV,increased CBV,decreased OEF,and normal CMRO_2.Low CBF_b(<31.8 mL/100mL/min,n=9)was associated with decreased CBF_b/CBV,increased CBV,increased OEF,and decreased CMRO_2.These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP,but partly includes highCBF_b regions with normal CPP,which has not been described in previous studies.展开更多
Local cerebral perfusion pressure(CPP) is a primary factor controlling cerebral circulation and previous studies have indicated that the ratio of cerebral blood flow(CBF) to cerebral blood volume(CBV) can be used as a...Local cerebral perfusion pressure(CPP) is a primary factor controlling cerebral circulation and previous studies have indicated that the ratio of cerebral blood flow(CBF) to cerebral blood volume(CBV) can be used as an index of the local CPP. In this study,we investigated whether the CBF/CBV ratio differs among different brain structures under physiological conditions, by means of O positron emission tomography. Nine healthy volunteers(5 men and 4women, mean age,47.0 ±1.2 years) were studied by H2 O bolus injection for CBF measurement and by C O inhalation for CBV measurement. The CBF/CBV ratio maps were created by dividing the CBF images by the CBV images after anatomical normalization.Regions of interest were placed on the CBF/CBV maps and comparing the regions. The mean CBF/CBV ratio was highest in the cerebellum(19.3 ± 5.2/min)' followed by the putamen(18.2 士 3.9), pons(16_4 土 4.6)' thalamus(14.5 土 3.3), cerebral cortices(13.2 土 2.4), and centrum semiovale(11.5 土 2.1).The cerebellum and putamen showed significantly higher CBF/CBV ratios than the cerebral cortices and centrum semiovale. We created maps of the CBF/CBV ratio in normal volunteers and demonstrated higher CBF/CBV ratios in the cerebellum and putamen than in the cerebral cortices and deep cerebral white matter. The CBF/CBV may reflect the local CPP and should be studied in hemodynamically compromised patients and in patients with risk factors for small-artery diseases of the brain.展开更多
Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis.In this study, we prepared mu...Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis.In this study, we prepared multifunctional microspheres loading ^(131)I-labeled hollow copper sulfide nanoparticles and paclitaxel( ^(131)I-HCu SNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats.18 F-fluordeoxyglucose(18 F-FDG) positron emission tomography/computed tomography(PET/CT) imaging detected that the expansion of the tumor volume was delayed(Po0.05) following intra-tumoral(i.t.) injection with ^(131)I-HCu SNPs-MS-PTX plus near-infrared(NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography(SPECT)/photoacoustic imaging mediated by ^(131)I-HCu SNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that ^(131)I-HCu SNPs-MS-PTX offered combined photothermal, chemo-and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, ^(131)I-HCu SNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.展开更多
Developing an objective biomarker for pain assessment is crucial for understanding neural coding mechanisms of pain in the human brain as well as for effective treatment of pain disorders.Neuroimaging techniques have ...Developing an objective biomarker for pain assessment is crucial for understanding neural coding mechanisms of pain in the human brain as well as for effective treatment of pain disorders.Neuroimaging techniques have been proven to be powerful tools in the ongoing quest for a pain signature in the human brain.Although there is still a long way to go before achieving a truly successful pain signature based on neuroimaging techniques,important progresses have been made through great efforts in the last two decades by the Pain Society.Here,we focus on neural responses to transient painful stimuli in healthy people,and review the relevant studies on the identification of a neuroimaging signature for pain.展开更多
基金supported by National Natural Science Foundation of China(Grant No.81202795)China Postdoctoral Science Foundation(Grant No.2015M571271)
文摘Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.
基金This study was reviewed and approved by the Institutional Review Board of National Institutes for Quantum Science and Technology,No.07-1064-28.No animals or animal-derived samples or patients or patient-derived samples were included in this study.
文摘BACKGROUND Radionuclides produce Cherenkov radiation(CR),which can potentially activate photosensitizers(PSs)in phototherapy.Several groups have studied Cherenkov energy transfer to PSs using optical imaging;however,cost-effectively identifying whether PSs are excited by radionuclide-derived CR and detecting fluorescence emission from excited PSs remain a challenge.Many laboratories face the need for expensive dedicated equipment.AIM To cost-effectively confirm whether PSs are excited by radionuclide-derived CR and distinguish fluorescence emission from excited PSs.METHODS The absorbance and fluorescence spectra of PSs were measured using a microplate reader and fluorescence spectrometer to examine the photo-physical properties of PSs.To mitigate the need for expensive dedicated equipment and achieve the aim of the study,we developed a method that utilizes a chargecoupled device optical imaging system and appropriate long-pass filters of different wavelengths(manual sequential application of long-pass filters of 515,580,645,700,750,and 800 nm).Tetrakis(4-carboxyphenyl)porphyrin(TCPP)was utilized as a model PS.Different doses of copper-64(^(64)CuCl_(2))(4,2,and 1 mCi)were used as CR-producing radionuclides.Imaging and data acquisition were performed 0.5 h after sample preparation.Differential image analysis was conducted by using ImageJ software(National Institutes of Health)to visually evaluate TCPP fluorescence.RESULTS The maximum absorbance of TCPP was at 390-430 nm,and the emission peak was at 670 nm.The CR and CRinduced TCPP emissions were observed using the optical imaging system and the high-transmittance long-pass filters described above.The emission spectra of TCPP with a peak in the 645-700 nm window were obtained by calculation and subtraction based on the serial signal intensity(total flux)difference between^(64)CuCl_(2)+TCPP and^(64)CuCl_(2).Moreover,the differential fluorescence images of TCPP were obtained by subtracting the^(64)CuCl_(2)image from the^(64)CuCl_(2)+TCPP image.The experimental results considering different^(64)CuCl_(2)doses showed a dosedependent trend.These results demonstrate that a bioluminescence imaging device coupled with different longpass filters and subtraction image processing can confirm the emission spectra and differential fluorescence images of CR-induced TCPP.CONCLUSION This simple method identifies the PS fluorescence emission generated by radionuclide-derived CR and can contribute to accelerating the development of Cherenkov energy transfer imaging and the discovery of new PSs.
文摘Background A medical content-based image retrieval(CBIR)system is designed to retrieve images from large imaging repositories that are visually similar to a user′s query image.CBIR is widely used in evidence-based diagnosis,teaching,and research.Although the retrieval accuracy has largely improved,there has been limited development toward visualizing important image features that indicate the similarity of retrieved images.Despite the prevalence of 3D volumetric data in medical imaging such as computed tomography(CT),current CBIR systems still rely on 2D cross-sectional views for the visualization of retrieved images.Such 2D visualization requires users to browse through the image stacks to confirm the similarity of the retrieved images and often involves mental reconstruction of 3D information,including the size,shape,and spatial relations of multiple structures.This process is time-consuming and reliant on users'experience.Methods In this study,we proposed an importance-aware 3D volume visualization method.The rendering parameters were automatically optimized to maximize the visibility of important structures that were detected and prioritized in the retrieval process.We then integrated the proposed visualization into a CBIR system,thereby complementing the 2D cross-sectional views for relevance feedback and further analyses.Results Our preliminary results demonstrate that 3D visualization can provide additional information using multimodal positron emission tomography and computed tomography(PETCT)images of a non-small cell lung cancer dataset.
基金Supported by a Grant-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science,and Technology,Japan,No.17K10460(to Aung W)
文摘AIM To investigate near-infrared photoimmunotherapeutic effect mediated by an anti-tissue factor(TF) antibody conjugated to indocyanine green(ICG) in a pancreatic cancer model.METHODS Near-infrared photoimmunotherapy(NIR-PIT) is a highly selective tumor treatment that utilizes an antibody-photosensitizer conjugate administration, followed by NIR light exposure. Anti-TF antibody 1849-ICG conjugate was synthesized by labeling of rat IgG2 b anti-TF monoclonal antibody 1849(anti-TF 1849) to a NIR photosensitizer,ICG. The expression levels of TF in two human pancreatic cancer cell lines were examined by western blotting. Specific binding of the 1849-ICG to TF-expressing BxPC-3 cells was examined by fluorescence microscopy. NIR-PITinduced cell death was determined by cell viability imaging assay. In vivo longitudinal fluorescence imaging was used to explore the accumulation of 1849-ICG conjugate in xenograft tumors. To examine the effect of NIRPIT, tumor-bearing mice were separated into 5 groups:(1) 100 μg of 1849-ICG i.v. administration followed by NIR light exposure(50 J/cm2) on two consecutive days(Days 1 and 2);(2) NIR light exposure(50 J/cm2) only on two consecutive days(Days 1 and 2);(3) 100 μg of 1849-ICG i.v. administration;(4) 100 μg of unlabeled antiTF 1849 i.v. administration; and(5) the untreated control. Semiweekly tumor volume measurements, accompanied with histological and immunohistochemical(IHC) analyses of tumors, were performed 3 d after the 2nd irradiation with NIR light to monitor the effect of treatments. RESULTS High TF expression in BxPC-3 cells was observed via western blot analysis, concordant with the observed preferential binding with intracellular localization of 1849-ICG via fluorescence microscopy. NIR-PIT-induced cell death was observed by performing cell viability imaging assay. In contrast to the other test groups, tumor growth was significantly inhibited by NIR-PIT with a statistically significant difference in relative tumor volumes for 27 d after the treatment start date [2.83 ± 0.38(NIR-PIT) vs 5.42 ± 1.61(Untreated), vs 4.90 ± 0.87(NIR), vs 4.28 ±1.87(1849-ICG), vs 4.35 ± 1.42(anti-TF 1849), at Day 27, P < 0.05]. Tumors that received NIR-PIT showed evidence of necrotic cell death-associated features upon hematoxylin-eosin staining accompanied by a decrease in Ki-67-positive cells(a cell proliferation marker) by IHC examination.CONCLUSION The TF-targeted NIR-PIT with the 1849-ICG conjugate can potentially open a new platform for treatment of TF-expressing pancreatic cancer.
文摘Many studies demonstrate that conventional anticancer drugs elevate intracellular level of reactive oxygen species(ROS) and alter redox-homeostasis of cancer cells. It is widely accepted that anticancer effect of these chemotherapeutics is due to induction of oxidative stress and ROS-mediated apoptosis in cancer. On the other hand, the harmful side effects of conventional anticancer chemotherapy are also due to increased production of ROS and disruption of redox-homeostasis of normal cells and tissues. This article describes the mechanisms for triggering and modulation of apoptosis through ROS-dependent and ROS-independent pathways. We try to answer the question: "Is it possible to induce highly specific apoptosis only in cancer cells, without overproduction of ROS, as well as without harmful effects on normal cells and tissues?" The review also suggests a new therapeutic strategy for selective killing of cancer cells, without significant impact on viability of normal cells and tissues, by combining anticancer drugs with redox-modulators, affecting specific signaling pathways and avoiding oxidative stress.
基金Supported by the National Natural Science Foundation of China,No.81501984 and No.81601377Tianjin Municipal Bureau of Health Science and Technology,No.2015KZ084 and No.2013KZ088Tianjin Medical University Science,No.2013KYQ07
文摘AIM To compare ^(18)F-fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma.METHODS Patients with newly diagnosed gastric lymphoma or gastric carcinoma who underwent ^(18)F-FDG PET/CT prior to treatment were included in this study. We reviewed and analyzed the PET/CT features of gastric wall lesions,including FDG avidity,pattern(focal/diffuse),and intensity [maximal standard uptake value:(SUVmax)]. The correlation of SUVmax with gastricclinicopathological variables was investigated by χ~2 test,and receiver-operating characteristic(ROC) curve analysis was performed to determine the differential diagnostic value of SUVmax-associated parameters in gastric lymphoma and gastric carcinoma. RESULTS Fifty-two patients with gastric lymphoma and 73 with gastric carcinoma were included in this study. Abnormal gastric FDG accumulation was found in 49 patients(94.23%) with gastric lymphoma and 65 patients(89.04%) with gastric carcinoma. Gastric lymphoma patients predominantly presented with type Ⅰ and type Ⅱ lesions,whereas gastric carcinoma patients mainly had type Ⅲ lesions. The SUVmax(13.39 ± 9.24 vs 8.35 ± 5.80,P < 0.001) and SUVmax/THKmax(maximal thickness)(7.96 ± 4.02 vs 4.88 ± 3.32,P < 0.001) were both higher in patients with gastric lymphoma compared with gastric carcinoma. ROC curve analysis suggested a better performance of SUVmax/THKmax in the evaluation of gastric lesions between gastric lymphoma and gastric carcinoma in comparison with that of SUVmax alone.CONCLUSION PET/CT features differ between gastric lymphoma and carcinoma,which can improve PET/CT evaluation of gastric wall lesions and help differentiate gastric lymphoma from gastric carcinoma.
基金the Tianjin Science and Technology Program Fund(grant No.18 PTZWHZ00100 and H2018206600).
文摘Objective:A high rate of unnecessary thymectomies has been reported.This study aimed to distinguish primary mediastinal lymphomas(PMLs)from thymic epithelial tumors(TETs)by evaluating volumetric and metabolic parameters with l8F-FDG PET/CT.Methods:A total of 136 patients who were pathologically diagnosed with TETs or PMLs were enrolled,and 18F-FDG PET/CT was performed before therapy.Volumetric parameters,including the mean SUV(SUVmean),metabolic tumor volume(MTV),total lesion glycolysis(TLG),and SUVmax,were determined and compared between the 2 subtypes.The diagnostic performance of these parameters was evaluated with receiver operating characteristic(ROC)curve analysis.Results:All parameters significantly differed between patients with PMLs and TETs.Patients with lymphomas were younger and had higher SUVmean,SUVmax,TLG,and MTV values than patients with TETs.The MTV and TLG values had similar diagnostic performance.ROC analysis indicated that the areas under the curves of the SUVmean and SUVmax values performed similarly(approximately 0.76)in differentiating patients with PMLs from TETs,and both values were better than the MTV and TLG values.When age was included with the SUVmax in differentiating TETs from PMLs,the AUC was 0.91,and the sensitivity and specificity increased to 80%and 93%,respectively.Conclusions:The SUVmax and volumetric parameters of 18F-FDG PET/CT can be used to distinguish patients with PMLs versus TETs,and thus may aid in preventing unnecessary thymectomies or other invasive operations.
文摘AIM:To present our initial experience with computed tomography guided radiofrequency ablation(RFA) of osteoid osteoma(OO) in our institution.METHODS:RFA was performed on eight patients(5 males and 3 females) with clinically and radiologically diagnosed OO(femoral neck,n = 4;femoral diaphysis,n = 2;tibial diaphysis,n = 1;fibular diaphysis,n = 1).Ablation was performed using an electrode with a 10-mm exposed tip for a total of 4-6 min at a targeted temperature of 90 degrees Celsius.No cooling system was used.The intervention was accepted as technically successful if the tip of the electrode could be placed within the center of the nidus.We defined clinical success as a disappearance within 2 wk after treatment of symptoms that had manifested at presentation.RESULTS:All procedures were technically successful.No major or immediate complications were observed.Clinical success was achieved in six of eight patients in the first procedure.A second procedure was performed for two patients who had recurrent or continued pain,and one of these cases was successfully treated.The overall rate of success was 87.5%(7/8).No complication was observed.CONCLUSION:Our preliminary results indicate a favorable success rate and no complications and are compatible with the previous reports of RFA of OO.
基金Supported by(partially)a Grant-in-Aid for Scientific Research(C)from the Ministry of Education,Culture,Sports,Science and Technology,Japan,No.17K10460 to Aung W
文摘AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer model.METHODS Phosphorylation of Akt, m TOR, the downstream effectors eukaryotic initiation factor 4 E binding protein 1(4 EBP1) and S6 ribosomal protein(S6) were evaluated in Bx PC-3 human pancreatic cancer cells treated with Yttrium-^(90)(^(90) Y) labeled anti-integrin α6β4 antibody(ITGA6 B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay. Therapeutic efficacy enhancement by oral BEZ235 administration was assessed using mice bearing Bx PC-3 xenograft tumors. Tumor volume measurements and immunohistochemical analyses(cell proliferation marker Ki-67, DNA damage marker p-H2 AX and p-4 EBP1 staining) of tumors were performed for evaluation of combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235, or each arm alone.RESULTS We found that phosphorylation of Akt(p-Akt), 4 EBP1(p-4 EBP1) and S6(p-S6) was inhibited by BEZ235. Colony formation in Bx PC-3 cells was additively suppressed by the combination of ^(90) Y-ITGA6 B4 and BEZ235. Pretreatment with BEZ235 before ^(90) Y-ITGA6 B4 exposure resulted in significant reduction of cells plating efficiency(PE)(0.54 ± 0.11 vs 2.81 ± 0.14 with 185 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01; 0.39 ± 0.08 vs 1.88 ± 0.09 with 370 k Bq/m L ^(90) Y-ITGA6 B4 exposure, P < 0.01) when 5 × 10~3 cells per dish were plated. In vivo, the combined treatment with ^(90) Y-ITGA6 B4 plus BEZ235 enhanced the inhibition of tumor growth and statistically significant differences of relative tumor volume were observed for 27 d after the treatment start date when compared with the ^(90) Y-ITGA6 B4 single injection treatment(1.03 ± 0.38 vs 1.5 ± 0.15 at Day 27, P < 0.05), and for 41 d when compared with the BEZ235 treatment alone(1.8 ± 0.7 vs 3.14 ± 1.19 at Day 41, P < 0.05). Tumors from treatment groups showed reduction in volumes, decreased Ki-67-positive cells, increased p-H2 AX-positive cells and decreased p-4 EBP1 expression. CONCLUSION The therapeutic efficacy of ^(90) Y-ITGA6 B4-RIT can be improved by combining with dual PI3 K and m TOR inhibitor, BEZ235, in a pancreatic cancer model suggesting potential clinical application.
基金supported by Tianjin Municipal Health Bureau Science and Technology Foundation(Grant No.16KG125)National Clinical Research Center for Cancer
文摘Extragonadal primary yolk sac tumor of the intestinal tract origin is exceedingly rare. Through a multiple disciplinary team, the diagnosis and treatment of primary intestinal yolk sac tumor were further defined. We report 2 such cases with detailed histologic and immunohistochemical analysis. The two patients were a 7-year-old girl and a 29-year-old woman. Both of them preoperatively had an elevated serum alpha fetoprotein(AFP) level(≥ 1,210 ng/mL). The tumors are located in the intestine and imaging examination indicated the rectum as the primary site. Grossly the mass was grey-white and crisp texture. Microscopic examination featured reticular, microcystic, macrocystic, papillary, solid, and some glandular patterns. Immunohistochemically,tumor cells of both cases were positive for SALL4, AFP, pan-cytokeratin(AE1/AE3), and glypican-3. Simultaneously, a stain for EMA, OCT4, CD30, HCG, vimentin and CK20 were negative in all 2 neoplasms. The features of morphology,immunohistochemistry, laboratory examinations and imaging studies consist of the diagnosis of primary yolk sac tumor of the intestine.
文摘Objective: Computed tomography (CT)-based attenuation correction (CTAC) offers the clear benefit of reliable reconstruction of single-photon emission computed tomography (SPECT) images through its ability to achieve object-specific attenuation maps, but artifacts from dense materials often deteriorate CTAC performance. Therefore, we investigate the feasibility of CTAC in the presence of dense materials using dual-energy virtual monochromatic CT data. Methods: A sodium pertechnetate-filled cylindrical uniform phantom, with a pair of undiluted iodine syringes attached, is scanned with a dual-source CT scanner to obtain both single-energy (120 kVp) polychromatic and dual-energy (80 kVp/140 kVp with tin filtering) virtual monochromatic CT images. The single-energy and the dual-energy CT images are then converted to attenuation maps at 141 keV. SPECT images are reconstructed from 99mTc emission data of the phantom using each single-energy and dual-energy attenuation map and incorporating CTAC procedure. A region-of-in- terest analysis is performed to quantitatively compare the attenuation maps between the single-energy and the dual-energy techniques, each at an iodine-free position and a position adjacent to the iodine solutions. Results: At the iodine-free position, the phantom provides a uniform distribution of attenuation maps in both the single-energy and the dual-energy techniques. In the presence of adjacent iodine solutions, however, severe artifacts appeare in the single-energy CT images. These artifacts make attenuation values fluctuate, resulting in erroneous pixel values in the CTAC SPECT images. In contrast, dual-energy CT strongly suppresses the artifacts and hence improves the uniformity of the attenuation maps and the resultant SPECT images. Conclusions: Dual-energy CT with virtual monochromatic reconstruction has the potential to substantially reduce artifacts arising from dense materials. It has the potential to improve the accuracy of attenuation maps and the resultant CTAC SPECT images.
文摘BACKGROUND Photodynamic therapy(PDT)is a minimally invasive form of cancer therapy,and the development of a novel photosensitizer(PS)with optimal properties is important for enhancing PDT efficacy.Folate receptor(FR)membrane protein is frequently overexpressed in 40%of human cancer and a good candidate for tumor-specific targeting.Specific active targeting of PS to FR can be achieved by conjugation with the folate moiety.A folate-linked,near-infrared(NIR)-sensitive probe,folate-Si-rhodamine-1(FolateSiR-1),was previously developed and is expected to be applicable to NIR-PDT.AIM To investigate the therapeutic efficacy of NIR-PDT induced by FolateSiR-1,a FRtargeted PS,in preclinical cancer models.METHODS FolateSiR-1 was developed by conjugating a folate moiety to the Si-rhodamine derivative through a negatively charged tripeptide linker.FR expression in the designated cell lines was examined by western blotting(WB).The selective binding of FolateSiR-1 to FR was confirmed in FR overexpressing KB cells(FR+)and tumors by fluorescence microscopy and in vivo fluorescence imaging.Low FR expressing OVCAR-3 and A4 cell lines were used as negative controls(FR-).The NIR light(635±3 nm)-induced phototoxic effect of FolateSiR-1 was evaluated by cell viability imaging assays.The time-dependent distribution of FolateSiR-1 and its specific accumulation in KB tumors was determined using in vivo longitudinal fluorescence imaging.The PDT effect of FolateSiR-1 was evaluated in KB tumor bearing mice divided into four experimental groups:(1)FolateSiR-1(100μmol/L)alone;(2)FolateSiR-1(100μmol/L)followed by NIR irradiation(50 J/cm2);(3)NIR irradiation(50 J/cm2)alone;and(4)no treatment.Tumor volume measurement and immunohistochemical(IHC)and histological examinations of the tumors were performed to analyze the effect of PDT.RESULTS High FR expression was observed in the KB cells by WB,but not in the OVCAR-3 and A4 cells.Substantial FR-specific binding of FolateSiR-1 was observed by in vitro and in vivo fluorescence imaging.Cell viability imaging assays showed that NIR-PDT induced cell death in KB cells.In vivo longitudinal fluorescence imaging showed rapid peak accumulation of FolateSiR-1 in the KB tumors 2 h after injection.In vivo PDT conducted at this time point caused tumor growth delay.The relative tumor volumes in the PDT group were significantly reduced compared to those in the other groups[5.81±1.74(NIR-PDT)vs 12.24±2.48(Folate-SiR-1),vs 11.84±3.67(IR),vs 12.98±2.78(Untreated),at Day 16,P<0.05].IHC analysis revealed reduced proliferation marker Ki-67-positive cells in the PDT treated tumors,and hematoxylin-eosin staining revealed features of necrotic-and apoptotic cell death.CONCLUSION FolateSiR-1 has potential for use in PDT,and FR-targeted NIR-PDT may open a new effective strategy for the treatment of FR-overexpressing tumors.
基金partly supported by the Molecular Imaging Program, a grant(21591561) from the Ministry of Education,Culture,Sports, Science,and Technology and the Japan Science and Technology Agency,Japanthe Research Promotion Program on Health from the National Institute of Biomedical Innovation,Japana Grant-in-Aid(H21-019 and H21-5) from the Ministry of Health, Welfare,and Labour,Japan
文摘Paradoxical reduction of cerebral blood flow(CBF)after administration of the vasodilator acetazolamide is the most severe stage of cerebrovascular reactivity failure and is often associated with an increased oxygen extraction fraction(OEF).In this study,we aimed to reveal the mechanism underlying this phenomenon by focusing on the ratio of CBF to cerebral blood volume(CBV)as a marker of regional cerebral perfusion pressure(CPP).In 37patients with unilateral internal carotid or middle cerebral arterial(MCA)steno-occlusive disease and8 normal controls,the baseline CBF(CBF_b),CBV,OEF,cerebral oxygen metabolic rate(CMRO_2),and CBF after acetazolamide loading in the anterior and posterior MCA territories were measured by^(15)O positron emission tomography.Paradoxical CBF_b reduction was found in 28 of 74 regions(18of 37 patients)in the ipsilateral hemisphere.High CBF_b(>47.6 mL/100 mL/min,n=7)was associated with normal CBF_b/CBV,increased CBV,decreased OEF,and normal CMRO_2.Low CBF_b(<31.8 mL/100mL/min,n=9)was associated with decreased CBF_b/CBV,increased CBV,increased OEF,and decreased CMRO_2.These findings demonstrated that paradoxical CBF reduction is not always associated with reduction of CPP,but partly includes highCBF_b regions with normal CPP,which has not been described in previous studies.
基金partly supported by the Molecular Imaging Program,a grant(21591561) from the Ministry of Education,Culture,Sports,Science,and Technology and the Japan Science and Technology Agency,Japanby the Research Promotion Program on Health from the National Institute of Biomedical Innovation,Japana Grant-in-Aid(H21-019 and H21-5) from the Ministry of Health,Welfare,and Labour,Japan
文摘Local cerebral perfusion pressure(CPP) is a primary factor controlling cerebral circulation and previous studies have indicated that the ratio of cerebral blood flow(CBF) to cerebral blood volume(CBV) can be used as an index of the local CPP. In this study,we investigated whether the CBF/CBV ratio differs among different brain structures under physiological conditions, by means of O positron emission tomography. Nine healthy volunteers(5 men and 4women, mean age,47.0 ±1.2 years) were studied by H2 O bolus injection for CBF measurement and by C O inhalation for CBV measurement. The CBF/CBV ratio maps were created by dividing the CBF images by the CBV images after anatomical normalization.Regions of interest were placed on the CBF/CBV maps and comparing the regions. The mean CBF/CBV ratio was highest in the cerebellum(19.3 ± 5.2/min)' followed by the putamen(18.2 士 3.9), pons(16_4 土 4.6)' thalamus(14.5 土 3.3), cerebral cortices(13.2 土 2.4), and centrum semiovale(11.5 土 2.1).The cerebellum and putamen showed significantly higher CBF/CBV ratios than the cerebral cortices and centrum semiovale. We created maps of the CBF/CBV ratio in normal volunteers and demonstrated higher CBF/CBV ratios in the cerebellum and putamen than in the cerebral cortices and deep cerebral white matter. The CBF/CBV may reflect the local CPP and should be studied in hemodynamically compromised patients and in patients with risk factors for small-artery diseases of the brain.
基金partially supported by National Natural Science Foundation of China (Nos. 81771861, 81471708, 81673018, 81530053, 81471685)the award of the "National Youth Thousand Talents Plan" of China, the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (No. 2012-05)+2 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (No. 20172010)2018 Shanghai Scientific and Technological Innovation Program(No. 18410711200)the Ph.D. Innovation Fund of Shanghai Jiao Tong University, School of Medicine (BXJ201821)
文摘Compared to conventional cancer treatment, combination therapy based on well-designed nanoscale platforms may offer an opportunity to eliminate tumors and reduce recurrence and metastasis.In this study, we prepared multifunctional microspheres loading ^(131)I-labeled hollow copper sulfide nanoparticles and paclitaxel( ^(131)I-HCu SNPs-MS-PTX) for imaging and therapeutics of W256/B breast tumors in rats.18 F-fluordeoxyglucose(18 F-FDG) positron emission tomography/computed tomography(PET/CT) imaging detected that the expansion of the tumor volume was delayed(Po0.05) following intra-tumoral(i.t.) injection with ^(131)I-HCu SNPs-MS-PTX plus near-infrared(NIR) irradiation. The immunohistochemical analysis further confirmed the anti-tumor effect. The single photon emission computed tomography(SPECT)/photoacoustic imaging mediated by ^(131)I-HCu SNPs-MS-PTX demonstrated that microspheres were mainly distributed in the tumors with a relatively low distribution in other organs. Our results revealed that ^(131)I-HCu SNPs-MS-PTX offered combined photothermal, chemo-and radio-therapies, eliminating tumors at a relatively low dose, as well as allowing SPECT/CT and photoacoustic imaging monitoring of distribution of the injected agents non-invasively. The copper sulfide-loaded microspheres, ^(131)I-HCu SNPs-MS-PTX, can serve as a versatile theranostic agent in an orthotopic breast cancer model.
基金supported by National Natural Science Foundation of China(No.81571659,No.81971694).
文摘Developing an objective biomarker for pain assessment is crucial for understanding neural coding mechanisms of pain in the human brain as well as for effective treatment of pain disorders.Neuroimaging techniques have been proven to be powerful tools in the ongoing quest for a pain signature in the human brain.Although there is still a long way to go before achieving a truly successful pain signature based on neuroimaging techniques,important progresses have been made through great efforts in the last two decades by the Pain Society.Here,we focus on neural responses to transient painful stimuli in healthy people,and review the relevant studies on the identification of a neuroimaging signature for pain.
