Histological Microvessel Density Research Articles

Assessment of tissue perfusion of pancreatic cancer as potential imaging biomarker by means of Intravoxel incoherent motion MRI and CT perfusion: correlation with histological microvessel density as ground truth

Background/objectivesThe aim of this study was to compare intravoxel incoherent motion (IVIM) diffusion weighted (DW) MRI and CT perfusion to assess tumor perfusion of pancreatic ductal adenocarcinoma (PDAC).MethodsIn this prospective study, DW-MRI and CT perfusion were conducted in nineteen patients with PDAC on the day before surgery. IVIM analysis of DW-MRI was performed and the parameters perfusion fraction f, pseudodiffusion coefficient D*, and diffusion coefficient D were extracted for tumors, upstream, and downstream parenchyma. With a deconvolution-based analysis, the CT perfusion parameters blood flow (BF) and blood volume (BV) were estimated for tumors, upstream, and downstream parenchyma. In ten patients, intratumoral microvessel density (MVDtumor) and microvessel area (MVAtumor) were analyzed microscopically in resection specimens. Correlation coefficients between IVIM parameters, CT perfusion parameters, and histological microvessel parameters in tumors were calculated. Receiver operating characteristic (ROC) analysis was performed for differentiation of tumors and upstream parenchyma.Resultsftumor significantly positively correlated with BFtumor (r = 0.668, p = 0.002) and BVtumor (r = 0.672, p = 0.002). There were significant positive correlations between ftumor and MVDtumor/ MVAtumor (r ≥ 0.770, p ≤ 0.009) as well as between BFtumor and MVDtumor/ MVAtumor (r ≥ 0.697, p ≤ 0.025). Correlation coefficients between ftumor and MVDtumor/ MVAtumor were not significantly different from correlation coefficients between BFtumor and MVDtumor/ MVAtumor (p ≥ 0.400). Moreover, f, BF, BV, and permeability values (PEM) showed excellent performance in distinguishing tumors from upstream parenchyma (area under the ROC curve ≥0.874).ConclusionsThe study shows that IVIM derived ftumor and CT perfusion derived BFtumor similarly reflect vascularity of PDAC and seem to be comparably applicable for the evaluation of tumor perfusion for tumor characterization and as potential quantitative imaging biomarker.Trial registrationDRKS, DRKS00022227, Registered 26 June 2020, retrospectively registered. https://www.drks.de/drks_web/navigate.do?navigationId=trial. HTML&TRIAL_ID=DRKS00022227.

The correlation between microvessel pathological changes of the endplate and degeneration of the intervertebral disc in diabetic rats.

[This retracts the article DOI: 10.3892/etm.2012.868.].

Delayed Contrast Enhancement in Magnetic Resonance Imaging and Vascular Morphology of Primary Diffuse Large B-Cell Lymphoma (DLBCL) of the Central Nervous System (CNS): A Retrospective Study.

BackgroundThis study aimed to compare the magnetic resonance imaging (MRI) findings of primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (CNS) with delayed contrast enhancement and histological microvessel density (MVD). T1-weighted and T2-weighted contrast-enhanced and non-enhanced brain imaging were used. CNS lymphoma tissue was evaluated using primary antibodies to endothelial cells and smooth muscle cells, and histochemical staining for reticulin fibers and basement membrane, which allowed quantification of the MVD.Material/MethodsTwenty-one patients with histologically confirmed primary DLBCL of the CNS underwent pre-contrast-enhanced and postcontrast-enhanced MRI. Histology of the CNS lymphoma tissue included immunohistochemical staining with antibodies to CD34 for vascular endothelial cells and alpha smooth muscle actin (ASMA) for vascular smooth muscle cells, and histochemical staining included periodic acid-Schiff (PAS) and silver staining for reticulin fibers to evaluate microvessel density (MVD).ResultsIn primary DLBCL of the CNS, a positive correlation was found between the degree of necrosis and the size of the lymphoma (r=0.546, P=0.01). Delayed imaging enhancement was significantly correlated with the number of mature vessels, MVD, basement membrane, and reticulin fibers (r=0.593, 0.466, 0.446 and 0.497, respectively). Standardized β regression coefficient analysis showed that the MVD, PAS-positive structures, the number of mature vessels, and reticulin fibers, were significantly associated with delayed enhancement on MRI (β values, 0.425, 0.409, 0.295, and 0.188, respectively).ConclusionsIn primary DLBCL of the CNS, delayed imaging enhancement on MRI may be due to reduced neovascularization and vascular infiltration by lymphoma cells.

Endorectal power Doppler ultrasonography is a reliable method for evaluation of rectal cancer angiogenesis.

We aimed to assess the preoperative rectal cancer angiogenesis with Endorectal Power Doppler Ultrasonography by using the Power Doppler Vascularity Index (PDVI) calculated by imaging analysis software, and to compare it with the microvessel density (MVD) in surgical specimens PATIENTS AND METHODS: This study included 110 patients (39 females; mean age 61.5 years) with rectal cancer. Immunohistochemical staining of surgical specimens with anti-CD-31 antibody was used for MVD evaluation. The PDVI of each tumor was calculated using Endorectal Power Doppler with computer-assisted quantification of colour pixels. Mean MVD - 163 ± 69 microvessels/mm2 (50-328) was used as a cutoff point, differentiating two groups of tumors with high (> 160 mm2) and low (≤ 160 mm2) angiogenic activity. Mean PDVI of 8.9 ± 6.0% (0-27.3) was used as a cutoff point, dividing two groups of tumors with high (> 8%) and low (≤ 8%) PDVI. The MVD and the PDVI showed a good positive correlation (r = 0.438, p = 0.002). Patients with low PDVI had 25 months longer overall survival (p < 0.05) than patients with high PDVI. Patients with low MVD had 36 months longer survival (p < 0.05). Endorectal Power Doppler Ultrasonography is a reliable and noninvasive method for assessment of the extent of rectal cancer angiogenesis. Tumor angiogenesis assessed by the PDVI correlated with histological MVD determination and could predict survival rates. Endorectal Power Doppler examination is a useful and reproducible method for in vivo preoperative quantitative assessment of tumor vascularization.

A Prospective Study on the Value of Ultrasound Microflow Assessment to Distinguish Malignant from Benign Solid Breast Masses: Association between Ultrasound Parameters and Histologic Microvessel Densities.

ObjectiveTo investigate the value of ultrasound (US) microflow assessment in distinguishing malignant from benign solid breast masses as well as the association between US parameters and histologic microvessel density (MVD).Materials and MethodsNinety-eight breast masses (57 benign and 41 malignant) were examined using Superb Microvascular Imaging (SMI) and contrast-enhanced US (CEUS) before biopsy. Two radiologists evaluated the quantitative and qualitative vascular parameters on SMI (vascular index, morphology, distribution, and penetration) and CEUS (time-intensity curve analysis and enhancement characteristics). US parameters were compared between benign and malignant masses and the diagnostic performance was compared between SMI and CEUS. Subgroup analysis was performed according to lesion size. The effect of vascular parameters on downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4A masses was evaluated. The association between histologic MVD and US parameters was analyzed.ResultsMalignant masses were associated with a higher vascular index (15.1 ± 7.3 vs. 5.9 ± 5.6), complex vessel morphology (82.9% vs. 42.1%), central vascularity (95.1% vs. 59.6%), penetrating vessels (80.5% vs. 31.6%) on SMI (all, p < 0.001), as well as higher peak intensity (37.1 ± 25.7 vs. 17.0 ± 15.8, p < 0.001), slope (10.6 ± 11.2 vs. 3.9 ± 4.2, p = 0.001), area (1035.7 ± 726.9 vs. 458.2 ± 410.2, p < 0.001), hyperenhancement (95.1% vs. 70.2%, p = 0.005), centripetal enhancement (70.7% vs. 45.6%, p = 0.023), penetrating vessels (65.9% vs. 22.8%, p < 0.001), and perfusion defects (31.7% vs. 3.5%, p < 0.001) on CEUS (p ≤ 0.023). The areas under the receiver operating characteristic curve (AUCs) of SMI and CEUS were 0.853 and 0.841, respectively (p = 0.803). In 19 masses measuring < 10 mm, central vascularity on SMI was associated with malignancy (100% vs. 38.5%, p = 0.018). Considering all benign SMI parameters on the BI-RADS assessment, unnecessary biopsies could be avoided in 12 category 4A masses with improved AUCs (0.500 vs. 0.605, p < 0.001). US vascular parameters associated with malignancy showed higher MVD (p ≤ 0.016). MVD was higher in malignant masses than in benign masses, and malignant masses negative for estrogen receptor or positive for Ki67 had higher MVD (p < 0.05).ConclusionUS microflow assessment using SMI and CEUS is valuable in distinguishing malignant from benign solid breast masses, and US vascular parameters are associated with histologic MVD.

Ultrafast Dynamic Contrast-Enhanced Breast MRI: Kinetic Curve Assessment Using Empirical Mathematical Model Validated with Histological Microvessel Density

To evaluate whether parameters from empirical mathematical model (EMM) for ultrafast dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) correlate with histological microvessel density (MVD) in invasive breast cancer. Ninety-eight consecutive patients with invasive breast cancer underwent an institutional review board-approved ultrafast DCE-MRI including a pre- and 18 postcontrast whole breast ultrafast scans (3 seconds) followed by four standard scans (60 seconds) using a 3T system. Region of interest was placed within each lesion where the highest signal increase was observed on ultrafast DCE-MRI, and the increase rate of enhancement was calculated as follows: ΔS = (SIpost - SIpre)/SIpre. The kinetic curve obtained from ultrafast DCE-MRI was analyzed using a truncated EMM: ΔS(t) = A(1 - e-αt), where A is the upper limit of the signal intensity, α (min-1) is the rate of signal increase. The initial slope of the kinetic curve is given by Aα. Initial area under curve (AUC30) and time of initial enhancement was calculated. From the standard DCE-MRI, the initial enhancement rate (IER) and the signal enhancement ratio (SER) were calculated as follows: IER = (SIearly - SIpre)/SIpre, SER = (SIearly - SIpre)/(SIdelayed - SIpre). The parameters were compared to MVD obtained from surgical specimens. A, α, Aα, AUC30, and time of initial enhancement significantly correlated with MVD (r = 0.29, 0.40, 0.51, 0.43, and -0.32 with p = 0.0027, p < 0.0001, p < 0.0001, p < 0.0001, and p = 0.0012, respectively), whereas IER and SER from standard DCE-MRI did not. The parameters of the EMM, especially the initial slope or Aα, for ultrafast DCE-MRI correlated with MVD in invasive breast cancer.

Comparison of microvascular perfusion evaluation among IVIM-DWI, CT perfusion imaging and histological microvessel density in rabbit liver VX2 tumors

ObjectTo explore microcirculation features with intravoxel incoherent motion (IVIM) and to compare IVIM with CT perfusion imaging (CTPI) and microvessel density (MVD). Materials and methodsHepatic CTPI and IVIM were performed in 16 rabbit liver VX2 tumor models. Hepatic arterial perfusion (HAP), hepatic arterial perfusion index (HPI), Blood flow (BF), and blood volume (BV) from CTPI were measured. Apparent diffusion coefficient (ADC), true diffusion coefficient (D), perfusion fraction (f), and pseudo-diffusion coefficient (D*) from IVIM were measured. MVD was counted with CD34 stain. The microcirculation features with IVIM were compared with CTPI parameters and MVD. ResultsStrong linear correlations were found between D value (0.89±0.21×10−3mm2/s) and HAP (15.83±6.97ml/min/100mg) (r=0.755, P=0.001) and between f value (12.64±6.66%) and BV (9.74±5.04ml/100mg) (r=0.693, P=0.004). Moderate linear correlations were observed between ADC (1.07±0.32×10−3mm2/s) and HAP (r=0.538, P=0.039), respectively; and between D value and MVD (9.31±2.57 vessels at 400×magnification) (r=0.509, P=0.044). No correlations were found between D* (119.90±37.67×10−3mm2/s) and HAP, HPI (68.34±12.91%), BF (4.95±2.16ml/min/100mg), BV. ConclusionIVIM parameters can characterize microcirculation to certain extent and separate it from pure water molecular diffusion. There is fair correlation between D or ADC value and CTPI parameters or MVD, but no correlation between D* or f value and CTPI parameters or MVD except f value and BV, which is still unclear and need further clinical studies to validate.

Use of Ultrasmall Superparamagnetic Iron Oxide Enhanced Susceptibility Weighted Imaging and Mean Vessel Density Imaging to Monitor Antiangiogenic Effects of Sorafenib on Experimental Hepatocellular Carcinoma.

We investigated effectiveness of ultrasmall superparamagnetic iron oxide enhanced susceptibility weighted imaging (USPIO-enhanced SWI) and mean vessel density imaging (Q) in monitoring antiangiogenic effects of Sorafenib on orthotopic hepatocellular carcinoma (HCC). Thirty-five HCC xenografts were established. USPIO-enhanced SWI and Q were performed on a 1.5 T MR scanner at baseline, 7, 14, and 21 days after Sorafenib treatment. Intratumoral susceptibility signal intensity (ITSS) and Q were serially measured and compared between the treated (n = 15) and control groups (n = 15). Both ITSS and Q were significantly lower in the treated group at each time point (P < 0.05). Measurements in the treated group showed that ITSS persisted at 7 days (P = 0.669) and increased at 14 and 21 days (P < 0.05), while Q significantly declined at 7 days (P = 0.028) and gradually increased at 14 and 21 days. In the treated group, significant correlation was found between Q and histologic microvessel density (MVD) (r = 0.753, P < 0.001), and ITSS correlated well with MVD (r = 0.742, P = 0.002) after excluding the data from baseline. This study demonstrated that USPIO-enhanced SWI and Q could provide novel biomarkers for evaluating antiangiogenic effects of Sorafenib on HCC.

Quantitative Analysis of Contrast-Enhanced Ultrasound Imaging in Invasive Breast Cancer: A Novel Technique to Obtain Histopathologic Information of Microvessel Density

We examined whether enhancement area ratios obtained by the new bubble detection method correlate with histologic microvessel density in invasive breast cancer. Forty consecutive patients with invasive breast cancer lesions underwent contrast-enhanced ultrasound. The ratio of enhanced area to manually segmented tumor area (enhancement area ratio) was obtained with the new method at peak and delayed phases (50–54, 55–59, 60–64 and 65–69 s). We also analyzed time–intensity curves to obtain peak intensity and area under curve. Enhancement area ratios in both peak and delayed phases (50–54, 55–59, 60–64 and 65–69 s) were significantly correlated with microvessel density (r = 0.57, 0.62, 0.68, 0.61 and 0.58; p = 0.0001, <0.0001, <.0001, <.0001 and 0.0001, respectively). In time–intensity curve analysis, peak intensity was significantly correlated (r = 0.43, p = 0.0073), whereas area under the curve was not (r = 0.29, p = 0.0769). Enhancement area ratios obtained by the new method were correlated with microvessel density in invasive breast cancer.

In vivo monitoring of angiogenesis during tendon repair: a novel MRI-based technique in a rat patellar tendon model

Recent in vivo studies were able to show the impairing effect of neoangiogenesis in degenerative tendon diseases. Clinical in vivo monitoring of angiogenesis in injured tendons therefore seems to be crucial for an accurate therapeutic approach. The aim of this study was to develop a novel magnetic resonance imaging (MRI)-based technique for observing angiogenesis during tendon healing in vivo. Tendinopathy was induced by an in situ freezing model of rat patellar tendon and monitored after 7, 14, and 28days. Animals were randomly divided into an imaging and immunohistochemical group. MRI with a 'blood pool' contrast agent was used to determine neoangiogenesis during tendon healing. MRI was compared to histochemical staining and quantification of blood vessels in injured and native tendons. MRI data revealed a peak in changes in the transverse relaxation rate (ΔR 2*), which is proportional to relative blood volume, 7days after surgery and decrease until day 28. Histological microvessel density and vascular endothelial growth factor synthesis were also most evident at day 7 and decreased over time. The current results are demonstrating a time-dependent correlation between microvessel density and ΔR 2*. Thus, MRI-based evaluation of angiogenesis in the tendon might be a new promising technique for in vivo monitoring of angiogenesis and therapy response in the future.

Tumor perfusion‐related parameter of diffusion‐weighted magnetic resonance imaging: Correlation with histological microvessel density

We obtained intravoxel incoherent motion (IVIM) parameters through biexponential analysis on diffusion-weighted MR imaging (DWI) using multiple b values. Correlation was evaluated between these parameters and histological microvessel density (MVD) for the possibility of noninvasive evaluation of MVD with DWI. Twenty-five nude mice with the HT29 colorectal cancer cells implanted were analyzed after undergoing DWI with multiple b values (0, 50, 100, 300, 500, 700, and 1000 s/mm(2)). Tissue diffusivity (D(t)), pseudo-diffusion coefficient (D(p)), and perfusion fraction (f(p)) were calculated using a biexponential analysis, and these parameters were correlated with MVD. The MVD was determined with the CD31 stain. For statistical analysis, Spearman's rank correlation was applied. The mean value and correlation coefficient with MVD for each IVIM parameter were as follows: D(t) = 0.98 ± 0.06 × 10(-3) mm(2)/s with r = 0.139 (P = 0.508); D(p) = 23.70 ± 7.94 × 10(-3) mm(2)/s with r = 0.782 (P < 0.001); and f(p) = 15.58 ± 5.7% with r = 0.749 (P < 0.001). D(p) and f(p) showed significant correlation with MVD, but D(t) did not. The IVIM parameters, D(p) and f(p), on DWI might be used in the noninvasive evaluation of MVD.

Abstract 1749: The downregulated expression of adiponectin receptors (AdipoR1, R2) in human colorectal cancer

Abstract [Background] Adiponectin is 30 kDa adipocytokine hormone secreted by the adipose tissues, which mediates antineoplastic as well as anti-angiogenic effects after binding to its receptors, Adipo-R1 and Adipo-R2, which has been reported to be expressed in colorectal cancer tissue and cell lines. Recent studies have shown decreased levels of adiponectin in sera of patients with various types of cancer, including colorectal. And a recent study demonstrated that adiponectin expression is significantly associated with high histological grade tumors and low microvessel density count in colorectal cancer, suggestive of an anti-angiogenic role for adiponectin in colorectal cancer. However, presently, the expression and function of adiponectin receptors in tumor tissue have not been well characterized. Thus, in the present study, we aimed to study the expression of adiponectin receptors in colorectal cancer tissues, and investigate on their clinicopathological implications. [Methods] Surgically resected specimens from 48 patients with colorectal cancer, receiving surgical operation in our surgical department in the period between November 2008 and July 2009, were analyzed. The study was approved by the Human Ethics Committee of the University of Tokyo. The messages and protein expressions of AdipoR1 and AdipoR2 were evaluated by real-time RT-PCR and immunohistochemistry, respectively, in cancer tissues and the matched normal counterparts. [Results] The mean age of the patients was 66.79±11.85 years. The levels of expression of both AdipoR1/AdipoR2, normalized with the internal control (beta-actin), were significantly lower in cancer specimens compared with normal mucosa (0.966±0.392, vs1.366±0.408, p&amp;lt;0.001 and 0.918±0.309, vs1.596±0.459, p&amp;lt;0.001, respectively for AdipoR1 and Adipo R2). The mRNA levels of AdipoR1 and AdipoR2 showed a tendency of decrease in tumors with nodal metastases and the difference was significant with AdipoR2 (p&amp;lt;0.05). Immunohistochemistry with polyclonal Abs showed a consistent reduction in protein expression of both receptors in cancer tissues in comparison with the normal counterparts. [Conclusion] Both receptors were downregulated in colorectal cancer, as confirmed by the mRNA and the protein expressions, and AdipoR2 seemed to be associated with nodal metastases. This downregulation seems to be associated with poorer prognosis of colorectal cancer, and may be an escape mechanism of cancer cells from the suppressive effects of adiponectin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1749.

Correlation of Quantified Contrast-Enhanced Sonography With In Vivo Tumor Response

The purpose of our study was to establish in vivo criteria for monitoring tumor treatment response using 3-dimensional (3D) volumetric gray scale, power Doppler, and contrast-enhanced sonography. Twelve mice were implanted with Lewis lung carcinoma cells on their hind limbs and categorized to 4 groups: control, chemotherapy, radiation therapy, and chemoradiation. A high-frequency ultrasound system with a 40-MHz probe was used to image the tumors. Follow-up contrast-enhanced sonography was performed on days 7 and 14 of treatment with two 50-microL boluses of a perflutren microbubble contrast agent injected into the tail vein. The following contrast-enhanced sonographic criteria were quantified: time to peak, peak intensity, alpha (microvessel cross-sectional area), and beta (microbubble velocity). Three-dimensional power Doppler images were also obtained after the acquisition of contrast data. On day 15, the tumors were excised for immunohistochemical analysis with CD31 fluorescent staining. The tumor size and 3D power Doppler vascular index showed no statistically significant correlation with microvascular density in all examined groups. Among all of the analyzed contrast-enhanced sonographic parameters, relative alpha showed the strongest correlation with the histologic microvessel density (Pearson r = 0.93; P < .01) and an independent association with the histologic data in a multiple regression model (beta = .93; R(2) = 0.86; P < .01). Of the various examined sonographic parameters, alpha has the strongest correlation with histologic microvessel density and may be the parameter of choice for the noninvasive monitoring of tumor angiogenic response in vivo.

Correlation of 16-slice spiral CT perfusion enhancement parameters and histological microvessel density with lymphatic involvement in peripheral lung cancer

Objective To evaluate the clinical value of CT perfusion (CTP) imaging for providing quantitative information about angiogenesis in patients with lung carcinoma and investigate the correlation of CTP enhancement parameters and histological microvessel density (MVD) with lymphatic involvement inperipheral lung carcinoma. Methods Fifty-three patients with pathology-proved peripheral lung carcinoma underwent CT perfusion scan before operation. The enhancement parameters of CTP were calculated based on the time-density curves (TDC) of fist pass phase. All cases were classified into two groups according to pathologic results: tumor with and without lymph node involvement. Two-sample t test was used for the statistics. The ROC curve was used to assess the efficiency of the enhancement parameters of CT perfusion and MVD for predicting lymphatic involvement. Results Tumors with lymph node involvement had significantly higher value of MVD than those without lymph node involvement (64.69±16.34 and 42.67± 16.78, respectively,t=4.84,P 52/0.74 mm~2 or PV>1.52 ml·min~(-1)·ml~(-1). Conclusion The CT perfusion PV and histological MVD have good correlation with lymph node involvement in peripheral lung carcinoma and are important predicting parameters before operation. Key words: Lung neoplasms; Neovascularization,pathologic; Lymphatic metastasis; Tomography,X-ray computed; ROC curve

Association between microvessel density and histologic grade in renal cell carcinomas

Angiogenesis seems to contribute to tumor growth and the development of metastases. There may be an association between the vascular density of individual tumors and their prognosis. In the present survey we studied 53 cases of renal cell carcinoma investigating possible relationship between histologic grade and microvessel density (MVD) measured by an image analysis system. According to our results MVD was significantly associated with the histologic grade, higher grades being accompanied with a higher MVD. Further studies are needed to investigate a possible connection of MVD with the prognostic role of grade in RCCs.

The use of vascular biomarkers and imaging studies in the early clinical development of anti‐tumour agents targeting angiogenesis

Recent findings about the pathomechanisms of tumour angiogenesis have led to new therapeutic options in the treatment of malignant tumours. During the development of anti-angiogenic drugs, reporting ranged from healing cancer to completely ineffective drugs. In 2003 the first anti-angiogenic drug was approved. Several anti-angiogenic drugs are still in the clinical phase of development. In contrast to identifying the maximal tolerable dose, determination of the optimal biological dose--reaching biological activity at lower doses--has become the main target in the early development of anti-angiogenic agents. This has been evaluated by different biomarker techniques. As a new standard in anti-tumour treatment, a better understanding of imaging in the treatment monitoring for anti-angiogenic agents is important. Studies of tumour angiogenesis by tissue sampling rely on invasive procedures, adequate sampling and painstaking estimation of histological microvessel density. Attempts to develop wound healing assays to correlate angiogenesis in wounds with angiogenesis in tumour have been made but are still considered invasive and correlation of healthy with malignant tissue is still of limited validity. Several soluble markers of tumour angiogenesis were detected in various malignant diseases and were evaluated for assessing their use as surrogate markers in tumour angiogenesis. Further, soluble markers were investigated for visualizing them as imaging tools. Combining both, new soluble markers and imaging techniques, developing anticancer drugs and monitoring of therapy success becomes a dynamic process in which finally the patients' individual response can be achieved soon. Time-consuming delays for anatomically based restaging procedures can be avoided. Characterization of soluble biomarkers as well as different imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging and positron emission tomography combined with or without CT are reviewed in this manuscript.

Lymphatic involvement of pulmonary carcinoma correlated to the enhancement patterns of dynamic contrast-enhanced MRI and histological microvessel density: ROC curve analysis

目的 探讨肺癌MRI动态增强模式和肿瘤微血管密度与肺癌淋巴结转移的关系及其价值.方法将58例原发性肺癌根据病理报告分为有淋巴结转移组和无淋巴结转移组,对所有病例行动态增强MR扫描,根据时间-信号强度曲线计算肺癌动态增强MRI参数,并对癌肿作微血管密度计数(MVD),分析上述数据与肺癌淋巴结转移的关系.结果肺癌淋巴结转移组(35例)的MVD及曲线最大增强线性斜率(SS)均高于无淋巴结转移组(23例)[MVD分别为(72.37±13.74)条/0.74 mm2、(42.61±16.18)条/0.74 mm2;SS分别为(5.05±1.16)%/s、(2.57±1.09)%/s](t值分别为7.521、8.157,P值均 3.8%/s或MVD值>63条/0.74 mm2作为强烈提示有淋巴结转移的可能性时,参数SS较MVD 具有更高的敏感度[分别为85.7%(30/35)、74.3%(26/35)]和诊断符合率[分别为87.9% (51/58)、82.8% (48/58)].2条ROC曲线下的面积AZSS、AZMVD分别为0.958、0.920,AZSS>AZMVD,但两者间的差异无统计学意义(P=0.09). 结论参数MVD与SS均与肺癌淋巴结转移存在密切的关系,可作为术前判断肺癌淋巴结转移的预测因子和判断预后指标,而且快速、无创的动态增强MRI方法较病理组织学方法更具有优越性。

Optical Tomography with Ultrasound Localization: Initial Clinical Results and Technical Challenges

Optical tomography with ultrasound localization utilizes co-registered ultrasound lesion structure information to guide optical imaging reconstruction. A hand-held probe consisting of a commercial ultrasound transducer and near infrared optical imaging sensors was used to simultaneously acquire ultrasound images and optical measurements. A dual-mesh scheme was used to map the ultrasound-visible lesions to finer-grid lesion regions and coarser-grid background regions for optical imaging reconstruction. As a result, optical imaging reconstruction was well-conditioned for inverse mapping of lesion hemoglobin concentration and blood oxygen saturation. Initial clinical results have shown that early stage invasive cancers may be distinguished by a two-fold greater total hemoglobin concentration compared with fibroadenomas and other benign lesions. Initial results of advanced cancers have shown that the hemoglobin distribution is highly distorted and heterogeneous and the distorted distributions correlate with histological microvessel density counts and could be used to assess chemotherapy response.

Utilizing Optical Tomography with Ultrasound Localization to Image Heterogeneous Hemoglobin Distribution in Large Breast Cancers

PURPOSE: Angiogenesis in advanced breast cancers is highly distorted and heterogeneous. Noninvasive imaging that can monitor angiogenesis may be invaluable initially for diagnosis and then for assessing tumor response to treatment. By combining ultrasound (US) and near-infrared (NIR) optical imaging, a reliable new technique has emerged for localizing and characterizing tumor angiogenesis within the breast. METHODS: This new technique employs a commercial US transducer coupled with an array of NIR optical fibers mounted on a hand-held probe. The US image is used for lesion localization and for guiding optical imaging reconstruction. Optical sensors are used for imaging tumor total hemoglobin distribution, which is directly related to tumor angiogenesis. RESULTS: Six large breast carcinomas were studied and microvessel density count was then performed on tissue samples obtained from these cancers. Two patients had locally advanced breast cancers and received neoadjuvant chemotherapy for 3 months. In one patient, before chemotherapy, the total hemoglobin distribution showed a high concentration at the cancer periphery; the distribution was later confined to the core area after 3 months of treatment. In another patient, as treatment progressed, the maximum hemoglobin concentration decreased from 255.3, to 147.5, to 76.9 wmol/I with an associated reduction in spatial extension. The other four patients had cancers of 2.0 to 3.0 cm in size and were imaged either at the time of core biopsy or definitive surgery. The histologic microvessel density counts from these tumor samples correlate to hemoglobin distributions with a correlation coefficient of 0.64 (P < .05). CONCLUSION: These initial results suggest that this new imaging technique may have great potential in imaging the heterogeneous vascular distribution of larger breast cancers in vivo and in monitoring treatment-related changes in angiogenesis during chemotherapy.

Tumor angiogenesis and dynamic CT in colorectal carcinoma: Radiologic-pathologic correlation

To investigate the correlation between microvessel density and spiral CT perfusion imaging in colorectal carcinoma. Thirty-seven patients, with histologically proven colorectal carcinoma, underwent water enema spiral CT scan. The largest axial surface of the primary tumor was searched on unenhanced spiral CT images. At this level, the enhanced dynamic scan series was acquired. Time-density curves (TDC) were created from the region of interest drawn over the tumor, target artery by Toshiba Xpress/SX spiral CT with perfusion functional software. Then the perfusion was calculated. Microvessel density (MVD) was evaluated using immunohistochemical staining of surgical specimens with anti-CD34, and then MVD was correlated with perfusion. MVD of colorectal carcinomas was 33.11-173.44, mean 87.28, and perfusion was 15.60-64.80 mL/min/100 g, mean 39.74 mL/min/100 g. MVD and perfusion were not associated with invasive depth, metastasis and disease stage, and they all decreased with increasing Dukes' stage, but no significant correlation was found between them (r = 0.18, P = 0.29). There is no significant correlation between MVD and perfusion. Neovascularizaton and perfusion are highly presented in early colorectal carcinoma. CT perfusion imaging may be more suited for assessing tumorigenesis in colorectal carcinoma than histological MVD technique.