Diffusion‐weighted MRI for monitoring tumor response to photodynamic therapy

Purpose:

To examine diffusion‐weighted MRI (DW‐MRI) for assessing the early tumor response to photodynamic therapy (PDT).

Materials and Methods:

Subcutaneous tumor xenografts of human prostate cancer cells (CWR22) were initiated in athymic nude mice. A second‐generation photosensitizer, Pc 4, was delivered to each animal by a tail vein injection 48 h before laser illumination. A dedicated high‐field (9.4 Tesla) small animal MR scanner was used to acquire diffusion‐weighted MR images pre‐PDT and 24 h after the treatment. DW‐MRI and apparent diffusion coefficients (ADC) were analyzed for 24 treated and 5 control mice with photosensitizer only or laser light only. Tumor size, prostate specific antigen (PSA) level, and tumor histology were obtained at different time points to examine the treatment effect.

Results:

Treated mice showed significant tumor size shrinkage and decrease of PSA level within 7 days after the treatment. The average ADC of the 24 treated tumors increased 24 h after PDT (P < 0.001) comparing with pre‐PDT. The average ADC was 0.511 ± 0.119 × 10^?3 mm²/s pre‐PDT and 0.754 ± 0.181 × 10^?3 mm²/s 24 h after the PDT. There is no significant difference in ADC values pre‐PDT and 24 h after PDT in the control tumors (P = 0.20).

Conclusion:

The change of tumor ADC values measured by DW‐MRI may provide a noninvasive imaging marker for monitoring tumor response to Pc 4‐PDT as early as 24 h. J. Magn. Reson. Imaging 2010;32:409–417. © 2010 Wiley‐Liss, Inc.

     

光动力疗法对鲜红斑痣皮肤血流量影响的研究

本文采用激光多普勒技术对５６例患者的鲜红斑痣区皮肤经ＰＤＴ治疗前和治疗后的血流量进行了定量测定，并与正常皮肤血流量进行了比较研究。证实了ＰＤＴ治疗鲜红斑痣作用的机制是破坏病变部位扩张畸型的毛细血管网，使患部异常升高的血流量明显下降，治疗部位血流量下降的程度与其异常颜色消退的程度呈较好的相关性。     

衍射增强成像与成像应用实验

目的:目前的常规X线医学成像是通过吸收衬度成像,但分辨率不够高,由于DEI采用相位衬度机制而不是依赖于物体的吸收,故适合弱吸收组织尤其是软组织成像。本实验旨在评价DEI在生物医学样品成像中的诊断价值。材料和方法:大鼠脏器样品切片,在BSRF的4W1A束线上进行DEI方法成像。首先扫描获得摇摆曲线,再选择摇摆曲线上不同位置进行成像,成像结果与常规吸收像进行对照,分辨率通过显微放大法获得。结果:图像能显示常规医学X成像方法无法显示的肝脏微细结构,分辨率达到微米。结论:DEI的优良分辨率和衬度将有望改进生物医学组织的影像诊断水平。     

In vivo high‐resolution magnetic resonance skin imaging at 1.5 T and 3 T

As a noninvasive modality, MR is attractive for in vivo skin imaging. Its unique soft tissue contrast makes it an ideal imaging modality to study the skin water content and to resolve the different skin layers. In this work, the challenges of in vivo high‐resolution skin imaging are addressed. Three 3D Cartesian sequences are customized to achieve high‐resolution imaging and their respective performance is evaluated. The balanced steady‐state free precession (bSSFP) and gradient echo (GRE) sequences are fast but can be sensitive to off‐resonance artifacts. The fast large‐angle spin echo (FLASE) sequence provides a sharp depiction of the hypodermis structures but results in more specific absorption rate (SAR). The effect of increasing the field strength is assessed. As compared to 1.5 T, signal‐to‐noise ratio at 3 T slightly increases in the hypodermis and almost doubles in the dermis. The need for fat/water separation is acknowledged and a solution using an interleaved three‐point Dixon method and an iterative reconstruction is shown to be effective. The effects of motion are analyzed and two techniques to prevent motion and correct for it are evaluated. Images with 117 × 117 × 500 μm³ resolution are obtained in imaging times under 6 min. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Evaluation of collagen alteration after topical photodynamic therapy (PDT) using second harmonic generation (SHG) microscopy--in vivo study in a mouse model

Topical photodynamic therapy (PDT) mediated by 5-aminolevulinic acid (ALA) has been used for the treatment of age-related skin lesions for therapeutic or cosmetic purposes. The modulation of collagen component and structure might play a significant role in influencing treatment outcomes of PDT. In this study, the effect of multi-session low dose ALA PDT on skin rejuvenation was examined in a hairless mouse model. Changes in collagen and skin texture were investigated by histological examination and in vivo second harmonic generation (SHG) microscopy. Results indicated that multi-session PDT could improve the collagen density and arrangement of skin tissue. SHG microscopy combined with quantitative collagen analysis could provide a useful tool for the evaluation of collagen alteration induced by ALA PDT.     

Mechanisms in photodynamic therapy: part one—photosensitizers, photochemistry and cellular localization

The use of non-toxic dyes or photosensitizers (PS) in combination with harmless visible light that is known as photodynamic therapy (PDT) has been known for over a hundred years, but is only now becoming widely used. Originally developed as a tumor therapy, some of its most successful applications are for non-malignant disease. In a series of three reviews we will discuss the mechanisms that operate in the field of PDT. Part one discusses the recent explosion in discovery and chemical synthesis of new PS. Some guidelines on how to choose an ideal PS for a particular application are presented. The photochemistry and photophysics of PS and the two pathways known as Type I (radicals and reactive oxygen species) and Type II (singlet oxygen) photochemical processes are discussed. To carry out PDT effectively in vivo, it is necessary to ensure sufficient light reaches all the diseased tissue. This involves understanding how light travels within various tissues and the relative effects of absorption and scattering. The fact that most of the PS are also fluorescent allows various optical imaging and monitoring strategies to be combined with PDT. The most important factor governing the outcome of PDT is how the PS interacts with cells in the target tissue or tumor, and the key aspect of this interaction is the subcellular localization of the PS. Examples of PS that localize in mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes are given. Finally the use of 5-aminolevulinic acid as a natural precursor of the heme biosynthetic pathway, stimulates accumulation of the PS protoporphyrin IX is described.     

Clinical usefulness of B-flow imaging in the diagnosis of superficial soft tissue tumors

B-flow imaging is a recently developed ultrasound technique that extends the B-mode imaging quality of blood flow, including high-frame-rate and high-spatial-resolution imaging. The purpose of the present study was to clarify the usefulness of B-flow for evaluation of the hemodynamics of superficial soft tissue tumors. All 33 cases of superficial soft tissue tumors were examined by both B-flow and Color/Power Doppler methods on the same plane. The B-flow images that were obtained were evaluated by comparison with corresponding Color/Power Doppler images. The following four items were compared and evaluated: (1) sensitivity to the detection of tumor vessels; (2) quality of background B-mode imaging; (3) frame rate; and (4) spatial resolution of tumor vessels. B-flow was somewhat inferior to Color/Power Doppler imaging in sensitivity to the detection of tumor vessels. B-flow was clearly inferior in the quality of background B-mode imaging. B-flow provided high-frame-rate imaging. The diameter of tumor vessels on B-flow imaging was clearly thinner than that on Color/Power Doppler images and appeared to indicate the true diameter of tumor vessels. By providing high-frame-rate imaging and high spatial resolution, B-flow makes it possible to clarify the precise vascular structure.     

Heating of the scrotum by high-field-strength MR imaging

Sterility can occur in mammals if spermatogenic tissue is acutely or chronically heated to levels equal to or greater than body temperature. High-field-strength MR imaging has been shown to elevate tissue temperatures, particularly if high levels of RF radiation are used. To determine if MR imaging above the recommended level for RF radiation is associated with heating of the scrotum, scrotal skin temperatures were measured in eight subjects immediately before and after MR imaging of the scrotum with a 1.5-T, 64-MHz MR scanner at mean whole-body average specific absorption rates ranging from 0.56 to 0.84 W/kg (mean, 0.72 W/kg). The average imaging time was 23 min. A statistically significant (p less than .01) increase in average scrotal skin temperature was associated with MR imaging (before MR imaging, 30.8 degrees C; after MR imaging, 32.3 degrees C). The largest change in temperature was 3.0 degrees C, and the highest temperature measured was 34.1 degrees C. MR imaging at relatively high specific absorption rates produced a statistically significant increase in average scrotal skin temperature. However, the recorded temperatures were below the threshold known to affect spermatogenesis in mammals.     

Fluorescence evaluations for porphyrin formation during topical PDT using ALA and methyl-ALA mixtures in pig skin models

BackgroundPhotodynamic Therapy (PDT) using Aminolevulinic acid (ALA) and derivative molecules as topical medication and as a precursor of protoporphyrin (PPIX), is limited due to low permeation through skin or efficiency in porphyrin production. This behavior affects the production and homogeneity of PPIX distribution on superficial skin and in the deeper skin layers. Many authors propose alternatives to solve this such as, modification in the ALA and derivativemolecules, modifying the chemical properties of emulsion external phase or incorporating a delivery system to the emulsion. The goal of this study is to discuss what proportion of ALA and Methyl aminolevulinate (MAL) on mixtures increase the amount and uniformity of PPIX formation at superficial skin by fluorescence evaluations.MethodsThe study was conducted in vivo using a pig skin model. PPIX production was monitored using fluorescence spectroscopy and widefield fluorescence imaging on skin surface. 20% of ALA and MAL cream were done mixing the following proportions: ALA, M2 (80% ALA–20% MAL), M3 (60% ALA–40% MAL), M4 (50% ALA–MAL), M5 (40% ALA–60% MAL), M6 (20% ALA–80% MAL) and MAL.ResultsMixtures M3, M4, and M5 showed the most PPIX production on skin by widefield fluorescence imaging and fluorescence spectroscopy in 3 h of incubation. These results suggest that 50% of ALA and MAL in the same mixture increase the PPIX production in amount, homogeneity and time production when compared to ALA and MAL. This has a positive impact on photodynamic damage optimizing the PDT treatment.     

光动力疗法治疗鲜红斑痣1216例临床分析

目的：分析比较血啉甲醚（HMME）与血卟啉衍生物（HpD)为光敏剂行光动力疗法（PDT）鲜红斑痣的临床疗效及副反应。材料与方法：鲜红斑痣患者1216例,粉红型13．2％,紫红型68．3％,增厚型18．4％。静脉注射HpD或HMME3－7mg/kg后给予铜蒸气激光、KTDS／532激光或氩离子激光照射,功率密度50－100mW/cm^2,能量密度90－540J／cm^2,随访观察。结果：HMME－PDT和HpD－PDT对各型鲜红斑痣均能有效地消除病变颜色,所随访的1632个病灶在2个月至9年的随访期内末见复发。治疗后反应有：局部水肿5－7天,部分患者有结痂或一过性色素沉着,皮肤暂时性光过敏反应。HpD－PDT组避光期30－90天,HMME－PDT组占光期7－14天,与HpD－PDT相比,HMME－PDT具有反应轻、愈合快、不衣反应少,安全度大、避光期短、色素沉着轻、护理容易、重复治疗间隔期短的特点。结论：HMME－PDT与HpD－PDT都能有效治疗各型鲜红斑痣,但HMME－PDT具有不良反应少、安全度大,避光期短、护理容易、重复治疗间隔期短等优点。     

Optical coherence tomography imaging of non-melanoma skin cancer undergoing photodynamic therapy reveals subclinical residual lesions

BackgroundPhotodynamic therapy with methyl aminolaevulinate (MAL–PDT) is a widely used non-invasive treatment modality for non-melanoma skin cancer (NMSC). The outcome of MAL–PDT is usually primarily evaluated clinically. Optical coherence tomography (OCT) is a non-invasive imaging technology based on interferiometry. OCT has been proven to provide high accuracy in identifying NMSC lesions and performing thickness measurements of thin tumours.ObjectivesTo describe the OCT morphology in in-vivo NMSC lesions during MAL–PDT treatment and to investigate the use of OCT in evaluating the response of MAL–PDT treated NMSC lesions.MethodsA total of 18 biopsy-proven basal cell carcinomas and actinic keratoses were monitored by OCT during 2 sessions of MAL–PDT treatment. At 3-months follow-up the patients were assessed both by OCT and clinically. If the clinical and OCT evaluation came to different conclusions on recurrence of the lesion, patients were followed more closely at clinical appointments for up to one year after the PDT treatment.ResultsAll lesions displayed at least one OCT characteristic before MAL–PDT treatment. At 3 months follow-up, recurrence was suspected clinically in 5/18 cases, with OCT in 7/18 cases. OCT correctly identified all of the partial responses also found by the clinical examinations. In both cases where recurrence was only found in OCT, this was subsequently confirmed by histology.ConclusionsOur study suggests that OCT identified 29% more recurrences than clinical examination alone. OCT can detect subclinical residual NMSC lesions after MAL–PDT treatment and may therefore be an accurate tool for early detection of residual lesional tissue.     

Skin fluorescence following photodynamic therapy with NPe6 photosensitizer

BackgroundThe second-generation photosensitizer NPe6 has strong anti-tumor effects with a much shorter photosensitive period than the first-generation photosensitizer Photofrin. Although photosensitive period has been reduced, skin photosensitivity is still a major side effect of photodynamic therapy (PDT). Therefore, we conducted a prospective study to investigate whether the NPe6 fluorescence intensity in skin after PDT could be measured effectively in human patients to improve the management of a patient's photosensitive period.MethodsThe NPe6 fluorescence measurements using a constructed fluorescence sensing system at the inside of the arm were acquired prior to and 5 and 10 min after NPe6 administration as well as at the time of PDT (4–5 h after administration), at discharge (2 or 3 days after PDT), and at 1 or 2 weeks after PDT. Participants were interviewed as to whether they had any complications at 2 weeks after PDT.ResultsNine male patients and one female patient entered this study. Nine patients were inpatients and one patient was an outpatient. All of the measurements of NPe6 fluorescence in the skin could be obtained without any complications. The spectral peak was detected at the time of discharge (2–3 days after administration) in most cases and it decreased at 1 or 2 weeks after PDT.ConclusionsThe fluorescence of NPe6 in the skin could be detected feasibly using the fluorescence sensing system in human patients. Measuring the relative concentration of NPe6 in the skin indirectly by measuring fluorescence intensity might be useful to predict the period of skin photosensitivity after PDT.     

Current status of PDT in the United States

The field of photodynamic therapy (PDT) continues to make significant progress in the United States of America (USA). There are currently about 23 recruiting interventional clinical studies designed to evaluate the safety and efficacy of PDT in adult patients, in the USA [1]. Skin cancer and lung cancer are the primary sites with four studies investigating PDT for the treatment of basal cell carcinoma (BCC), one study using PDT to treat non-melanoma skin cancer in patients with solid organs transplant, three evaluating PDT in the treatment of actinic keratosis, and another study aims to treat acne. Three studies evaluating PDT in the treatment of non-small cell lung cancer with pleural disease, two of these studies include malignant mesothelioma, and one targeting locally advanced and metastasis that induce airway obstruction. In other disease sites there is one study that evaluates PDT in the treatment of head and neck cancer, non-muscle invasive bladder cancer, pancreatic cancer, esophageal cancer, anal cancer, prostate cancer or low-grade upper tract urothelial cancer. One study evaluates PDT in the treatment neurofibromatosis type 1, and one study evaluates the safety and feasibility of PDT to sterilize deep tissue abscess cavities.Several photosensitizers are being used with investigational new drug approval or exemption by the USA food and drug administration (FDA) [1]. The FDA-approved porfimer sodium is being used to treat locally advanced lung cancer or lung cancer with pleural disease, malignant central airway obstruction, malignant mesothelioma, and head and neck cancer. The topical pro-drug, aminolevulinic acid (ALA) is being used to treat BCC and anal cancer, while one study adds 4% imipramine cream to ALA PDT to treat microvesicle particle in the skin. A vascular drug, padeliporfin dipotassium, is being evaluated in the treatment of early-stage prostate cancer and low-grade upper tract urothelial cancer. A ruthenium polypyridyl complex administered by instillation is being evaluated for efficacy in treating non-muscle invasive bladder cancer. Verteporfin is being evaluated for efficacy in the treatment of pancreatic cancer. The safety and feasibility of PDT with methylene blue is being evaluated for sterilizing deeply seated abscess cavities.Treatment planning and dosimetry are being employed by measuring light dose rate (irradiance) and dose (fluence), as well as singlet oxygen. There is no system that is currently approved for clinical use in the USA. The National Institutes of Health supports about 40 investigators-initiated projects in the USA [2]. Most of these projects focus on developing novel methods to improve the response to PDT. These include advanced treatment planning and dosimetry systems, imaging using photoacoustic or theranostic approaches, combination therapies that utilize PDT to enhance the response to chemotherapy, use of Vitamin D to improve treatment outcomes and employing molecular targeted probes and functional nanoparticles and liposomes.Acknowledgement: Thanks to Dr. Sherri McFarland for her constructive suggestions and comments.Conflict of interest: Dr. Shafirstein is a co-inventor of the optical surface applicator and dosimetry system (USPTO 11,344,742, 11,040,217). He acknowledges current service on a scientific advisory board with honoraria and stock options from Lumeda Inc.; receiving grant support from Lumeda Inc.; receiving in-kind contributions from Pinnacle Biologics Inc., and grant support from Johnson and Johnson Enterprise Innovation, Inc.     

北京同步辐射装置(BSRF)医学成像实验研究

目的 探讨同步辐射技术用于医学成像的应用价值。方法 利用同步辐射光源的空间相干性、准直性、高亮度等特性进行成像实验。在北京同步辐射装置（BSRF）的4W1A束线上，使用衍射增强技术（DEI）对肝、肾等组织进行成像，部分结果与病理结果进行对照；使用白光技术对大鼠冠状动脉进行成像。2种技术的分辨率通过显微放大法获得。结果 成像结果均具有较高的衬度和分辨率，显微放大法获得的分辨率为微米量级。通过白光技术获得的大鼠心脏冠状动脉图像可显示到二级分支结构，部分可达三级结构。结论 DEI和白光技术等同步辐射成像技术可显示弱吸收组织及血管等微细结构，具有较好的应用前景。     

Periodic Mesoporous Ionosilica Nanoparticles: Versatile Nano-objects for Imaging,Photodynamic Therapy,Drug Delivery and siRNA Gene Silencing

We report the use of Periodic Mesoporous Ionosilica Nanoparticles (PMINPs) as versatile nano-objects for imaging, photodynamic therapy (PDT), drug delivery and efficient adsorption and delivery of siRNA into breast cancer cells. The synthesized mesoporous ionosilica nanoparticles are well known for several advantages: high specific area and uniformity of both size and shape of pores^[1]. In order to confer to these nanoparticles PDT and siRNA photochemical internalization (PCI) properties, a porphyrin derivative was integrated into the ionosilica framework.Our results indicate the formation of highly porous nanorods. A significant PDT effect was observed for both one-photon^[2] and two-photon excitation PDT, due to an important ROS production upon light irradiation in nanoparticles treated-breast cancer cells. Zeta potential measurements of PMINPs revealed the presence of positive surface charges which promoted the adsorption of siRNA and BODIPY molecules. The electrostatic complexation of siRNA was then verified by electrophoresis gel retardation assay. Furthermore, PMINPs formed stable complexes with siRNA (up to 24 hours) and were efficiently internalized into the cells after 4 hours incubation mostly with energy-dependent endocytosis process. The PCI effect was obvious under light irradiation and successfully led to luciferase gene silencing in luciferase-expressing breast cancer cells, while no gene silencing effect was observed in the absence of light. The dual effect of gene silencing by siRNA and PDT was also studied and revealed the existence of a synergistic effect.This work highlights the potential of porphyrin-doped ionosilica nanoparticles as multifunctional drug nanocarriers for nucleic acids, such as siRNA, with a triple ability to perform imaging, PDT and PCI.     

X-ray phase-contrast tomosynthesis for improved breast tissue discrimination

Purpose

Attenuation-based tomosynthesis has proven to successfully resolve the glandular tissue overlap present in mammography. However, the ability of tomosynthesis to differentiate tumorous and glandular tissue remains limited, due to the small differences in X-ray attenuation in breast tissue. One possibility to overcome this limitation and to further increase the diagnostic value of tomosynthesis exams, is the application of recently developed grating-based phase-contrast methods, which provide complementary information on the phase shift and the local scattering power of the sample. In this study, we report on first phase-contrast breast tomosynthesis results of a mastectomy sample slice with an invasive ductal carcinoma.

Material and methods

A slice of a mastectomy sample with histologically proven invasive ductal cancer was imaged at the synchrotron radiation source ESRF (Grenoble, France). We used a two-grating interferometer setup at the ninth fractional Talbot distance and with an X-ray energy of 23 keV. In grating interferometry absorption, differential phase, and scattering images are recorded simultaneously. The tomosynthesis scan comprises 61 projections. Multimodal tomosynthesis results were reconstructed using a standard filtered back-projection approach. Our findings are supported by a comparison of tomographic views to histopathology.

Results

Phase-contrast tomosynthesis combines the advantage of improved soft-tissue discrimination in phase-contrast imaging with the ability of tomosynthesis to provide a third dimension so that improved feature visibility is not hampered by superposition artifacts. Our results indicate superior diagnostic value due to the depth resolution supplied in tomosynthesis imaging; a region of necrotic tissue that is obscured in a projection image can clearly be depicted in one single tomosynthesis slice. Compared to absorption tomosynthesis alone, soft tissue contrast is significantly enhanced in phase-contrast tomosynthesis views, where fibrous structures are clearly visible.

Conclusion

In this article we present the first proof-of-principle grating-based phase-contrast tomosynthesis of a mastectomy sample section. A comparison of conventional attenuation with phase-contrast and dark-field tomosynthesis indicates that complementary information from three signals yields an increase in diagnostic value, which is verified in a comparison of our results to histological sections of the sample. As grating-based phase-contrast mammography efficiently works with conventional lab sources, our benchmark results indicate the potential benefit of translating phase-contrast tomosynthesis into a clinical setting.     

Triple-negative breast cancer treatment in xenograft models by bifunctional nanoprobes combined to photodynamic therapy

Triple-negative breast cancer (TNBC) overexpresses the Epidermal Growth Factor Receptor (EGFR), a characteristic of different types of tumors, linked to worse disease prognosis and risk of recurrence. Conventional treatments are also aggressive and can be morbid.. Therefore, t improvement and development of new methods are notorious. Photodynamic Therapy (PDT) is an effective method for treating different types of cancer by using light radiation to activate a photosensitizing agent (drug) in molecular oxygen presence, promoting cell death., Improving drug uptake in target cells could contribute to PDT efficiency. Accordingly, we developed a bifunctional nanoprobe (BN), used in PDT as a a treatment method in vivo against breast cancer. The BN uses gold nanoparticles with active targeting through the Epidermal Growth Factor (EGF) protein and Chlorine e6 (Ce6) carriers. We evaluated the therapeutic efficacy of in vivo xenograft in 4 groups: Saline, BN, Ce6+PDT, and BN+PDT. As a result, we observed that the BN+PDT group exhibited an excellent effect with greater selectivity to tumor tissue and tissue damage when compared to the Saline, BN, and Ce6+PDT groups. The results indicate a potential impact on breast cancer treatment in vivo.. In conclusion, our data propose that the BN developed heightened PDT efficacy through cellular DNA repair effects and tumor microenvironment.     

Differentiation of cysts from solid tumors in the breast with diffuse optical tomography

RATIONALE AND OBJECTIVES: Near-infrared diffuse optical tomography (DOT) is an emerging imaging technology that has the potential to offer enhanced contrast resolution over the existing technologies for detection and diagnosis of breast cancer. Thus far, the clinical evaluation of DOT has been largely limited to solid tumors. A pilot clinical study focused on DOT imaging of breasts with cysts is presented. MATERIALS AND METHODS: Six cases were studied using the recently developed compact, parallel-detection DOT system. Images characterizing the tissue absorption and scattering were obtained with a finite element-based reconstruction algorithm. The optical images were compared with the mammograms and sonograms. In one case, in vitro measurements of optical properties were conducted for the fluid obtained from needle aspiration. RESULTS: Substantial contrast between cyst and adjacent parenchyma is observed. For the six cases evaluated, the locations and sizes of cysts imaged optically are accurate and consistent with the mammographic and sonographic findings. For the case that aspiration was performed, the absorption and scattering coefficients imaged in the cyst region are quantitatively accurate compared with that measured in vitro from the fluid aspirated. CONCLUSION: This pilot study shows that cysts ranging from 1-4 cm in diameter can be quantitatively imaged. They can be differentiated from solid breast tumors because cysts generally demonstrate lower absorption and scattering coefficients compared with the surrounding normal tissue, whereas solid tumors show concurrent higher absorption and scattering related to the normal tissue.     

Distinguishing breast skin lesions from superficial breast parenchymal lesions: diagnostic criteria, imaging characteristics, and pitfalls

Superficial lesions are commonly encountered in the breast and may be located in the dermis, hypodermis (subcutaneous fat), or parenchyma. The differential diagnosis varies for each anatomic layer. Dermal lesions that are seen by breast imagers are usually benign skin cysts. Hypodermal lesions, although usually benign, may include lesions that arise from anterior terminal duct lobular units and include papilloma, adenosis, fibroadenoma, and breast cancer. To avoid misclassifying a small superficial breast cancer as a benign dermal lesion, it is necessary to understand superficial breast and skin anatomy and the mammographic, ultrasonographic (U.S.), and magnetic resonance (MR) imaging signs that indicate that a lesion is dermal. Mammography is the optimal modality for localizing calcifications to the dermis or hypodermis. However, U.S. typically has higher resolution for localizing masses than mammography and MR imaging. At US, a lesion may be categorized as dermal (a) if it is contained entirely within the dermis, (b) if a tract that extends from the lesion to the skin is seen, or (c) if a claw of tissue surrounding the margin of the lesion is present. As with other breast lesions, suspicious imaging features should be sought in addition to determining the anatomic origin. If histologic analysis is necessary to characterize lesions with an unknown cause or origin, precautions must be taken to decrease patient morbidity.