Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection, and virtually all cases of cervical cancer are attributable to infection by a subset of HPVs (reviewed in ref. 1). Despite the high incidence of HPV infection and the recent development of a prophylactic vaccine that confers protection against some HPV types, many features of HPV infection are poorly understood. It remains worthwhile to consider other interventions against genital HPVs, particularly those that target infections not prevented by the current vaccine. However, productive papillomavirus infection is species- and tissue-restricted, and traditional models use animal papillomaviruses that infect the skin or oral mucosa. Here we report the development of a mouse model of cervicovaginal infection with HPV16 that recapitulates the establishment phase of papillomavirus infection. Transduction of a reporter gene by an HPV16 pseudovirus was characterized by histology and quantified by whole-organ, multispectral imaging. Disruption of the integrity of the stratified or columnar genital epithelium was required for infection, which occurred after deposition of the virus on the basement membrane underlying basal keratinocytes. A widely used vaginal spermicide, nonoxynol-9 (N-9), greatly increased susceptibility to infection. In contrast, carrageenan, a polysaccharide present in some vaginal lubricants, prevented infection even in the presence of N-9, suggesting that carrageenan might serve as an effective topical HPV microbicide.
Multiparametric MR imaging (T2-weighted MR imaging, MR spectroscopy, dynamic contrast-enhanced MR imaging) of the prostate at 3 T enables tumor detection, with reasonable sensitivity and specificity values.
Purpose
To determine the prostate cancer detection rate of multi-parametric (MP) MRI at 3T. Precise one to one histopathologic correlation with MRI was possible using prostate MRI based custom-printed specimen molds following radical prostatectomy.
Materials and methods
This IRB approved prospective study included forty-five patients (mean age 60.2 years, range 49–75 years) with a mean PSA of 6.37ng/mL (range 2.3–23.7ng/mL), who had biopsy proven prostate cancer (mean Gleason score of 6.7; range 6 to 9). Prior to prostatectomy, all patients underwent prostate MRI on a 3T scanner which included tri-plane T2 weighted MRI, apparent diffusion coefficient maps of diffusion weighted MRI, dynamic contrast enhanced MRI, and spectroscopy.. The prostate specimen was whole mount sectioned in the mold allowing geometric alignment to MRI. Tumors were mapped on MRI and histopathology.. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI for cancer detection were calculated. Additionally, the effects of tumor size and Gleason score on sensitivity of MP-MRI were evaluated.
Results
PPV of MP-MRI to detect prostate cancer was 98%, 98%, and 100% in overall prostate, peripheral zone, and central gland, respectively. Sensitivities of MRI sequences were higher for tumors >5mm in diameter, as well as for tumors with higher Gleason scores (>7) (p<0.05).
Conclusion
Prostate MRI at 3T allows for the detection of prostate cancer. A multi-parametric approach increases the predictive power of MRI for diagnosis. In this study, accurate correlation between MP-MRI and histopathology was obtained by the patient specific MRI-based mold technique.
Homozygous loss of BHD may initiate renal tumorigenesis in the mouse. The conditional BHD knockout mouse may be a useful research model for dissecting multistep kidney carcinogenesis, and rapamycin may be considered as a potential treatment for Birt-Hogg-Dubé syndrome.
Purpose:To investigate whether apparent diffusion coefficients (ADCs) derived from diffusion-weighted (DW) magnetic resonance (MR) imaging at 3 T correlate with the clinical risk of prostate cancer in patients with tumors that are visible on MR images, with MR imaging/transrectal ultrasonography (US) fusion-guided biopsy as a reference.
Materials and Methods:Forty-eight consecutive patients (median age, 60 years; median serum prostate-specifi c antigen value, 6.3 ng/mL) who underwent DW imaging during 3-T MR imaging with an endorectal coil were included in this retrospective institutional review board-approved study, and informed consent was obtained from each patient. Patients underwent targeted MR imaging/transrectal US fusion-guided prostate biopsy. Mean ADCs of cancerous target tumors were correlated with Gleason and D'Amico clinical risk scores. The true risk group rate and predictive value of the mean ADC for classifying a tumor by its D'Amico clinical risk score was determined by using linear discriminant and receiver operating characteristic analyses.
Results:A signifi cant negative correlation was found between mean ADCs of tumors in the peripheral zone and their Gleason scores ( P = .003; Spearman r = 2 0.60) and D'Amico clinical risk scores ( P , .0001; Spearman r = 2 0.69). ADC was found to distinguish tumors in the peripheral zone with intermediate to high clinical risk from those with low clinical risk with a correct classifi cation rate of 0.73.
Conclusion:There
A novel PAMAM dendrimer-based nanoprobe for dual magnetic resonance and fluorescence imaging modalities was synthesized. Fluorescence studies revealed that Gd(III) complexation to the probe has no effect on the quantum yield; however, increases in the dye content resulted in partial quenching. The potential of the new nanoprobe, G6-(Cy5.5)(1.25)(1B4M-Gd)(145), as a dual modality imaging agent was demonstrated in vivo by the efficient visualization of sentinel lymph nodes in mice by both MRI and fluorescence imaging modalities.
MRI of the prostate performed at 3 T using an endorectal coil produces high-quality T2-weighted images; however, specificity for prostate cancer is improved by also performing dynamic contrast-enhanced MRI and using pharmacokinetic parameters, particularly K(trans) and k(ep), for analysis. These results are comparable to published results at 1.5 T.
Angiogenesis has long been established as a key element in the pathophysiology of tumor growth and metastasis. Increasingly, new molecularly targeted antiangiogenic drugs are being developed in the fight against cancer. These drugs bring with them a need for an accurate means of diagnosing tumor angiogenesis and monitoring response to treatment. Imaging techniques can offer this in a noninvasive way, while also providing functional information about the tumor. Among the many clinical imaging techniques available, MRI alone can provide relatively good spatial resolution and specificity, without ionizing radiation and with limited side effects. Arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) imaging techniques can be employed to confer indirect measures of angiogenesis, such as blood flow and blood volume, without the need for external contrast agents. Dynamic contrast-enhanced (DCE)-MRI is rapidly emerging as a standard method for directly measuring angiogenesis during angiogenesis-inhibitor drug trials. As macromolecular MR contrast agents become available, they will inevitably be utilized in the assessment of tumor perfusion and vessel permeability. Meanwhile, technological advances have made imaging at a molecular level a possibility. They have brought the potential to directly target MR contrast agents to markers of angiogenesis, such as the ␣ v  3 integrin. Before this is used clinically, however, substantial gains in sensitivity brought about by improved coils, pulse sequences, and contrast agents will be needed. Herein we discuss the techniques currently available for MRI of angiogenesis, along with their respective advantages and disadvantages, and what the future holds for this evolving field of imaging.
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