Lymphatic Drainage Pathways Research Articles

Unraveling Pancreatic Segmentation.

Limited pancreatic resections are increasingly performed, but the rate of postoperative fistula is higher than after classical resections. Pancreatic segmentation, anatomically and radiologically identifiable, may theoretically help the surgeon removing selected anatomical portions with their own segmental pancreatic duct and thus might decrease the postoperative fistula rate. We aimed at systematically and comprehensively reviewing the previously proposed pancreatic segmentations and discuss their relevance and limitations. PubMed database was searched for articles investigating pancreatic segmentation, including human or animal anatomy, and cadaveric or surgical studies. Overall, 47/99 articles were selected and grouped into 4 main hypotheses of pancreatic segmentation methodology: anatomic, vascular, embryologic and lymphatic. The head, body and tail segments are gross description without distinct borders. The arterial territories defined vascular segments and isolate an isthmic paucivascular area. The embryological theory relied on the fusion plans of the embryological buds. The lymphatic drainage pathways defined the lymphatic segmentation. These theories had differences, but converged toward separating the head and body/tail parts, and the anterior from posterior and inferior parts of the pancreatic head. The rate of postoperative fistula was not decreased when surgical resection was performed following any of these segmentation theories; hence, none of them appeared relevant enough to guide pancreatic transections. Current pancreatic segmentation theories do not enable defining anatomical-surgical pancreatic segments. Other approaches should be explored, in particular focusing on pancreatic ducts, through pancreatic ducts reconstructions and embryologic 3D modelization.

Imaging of lymphatic drainage from the chest and regional lymph nodes in lymphadenopathies of various etiologies

Introduction and aim. Chest lymphadenopathy is unspecific syndrome found in various diseases. The aim of the study was to give an overview of chest lymph outflow pathways and methods of chest lymphadenopathy imaging. Methods. 60 literature sources were analyzed: 28 in Russian and 32 in international journals. Various radiological methods of chest lymphadenopathy were analyzed as well. Results. A definition of lymphadenopathy, brief description of the chest lymphatic drainage pathways anatomy and modern classification of thoracic lymph nodes are provided in this article. Modern imaging methods of lymphatic drainage and thoracic lymph nodes in lymphadenopathy syndrome are presented: the traditional x-ray techniques, ultrasound, computed tomography, magnetic resonance imaging, SPECT, PET/CT. Conclusion. A problem of chest lymph outflow pathway studying and a problem of chest lymphadenopathy is significant and awaits further investigation. Optimal methods of chest lymphadenopathy imaging are anatomical (CT, US) and functional (SPECT, PET/CT).

Precise intraoperative sentinel lymph node biopsies guided by lymphatic drainage in breast cancer.

The purpose of this study was to present a novel surgical method for intraoperative precise sentinel lymph node biopsy (SLNB) and to determine its clinical efficacy and sensitivity in breast cancer patients. The sentinel lymph nodes (SLNs) were preoperatively evaluated by axillary ultrasound. The intraoperative detection of SLNs was guided by lymphatic drainage pathway. The lymphatic vessels and SLNs were visualized. During operation, we searched for all the true SLNs (trSLNs), para-SLNs (paSLNs) and post-SLNs (poSLNs) followed lymphatic drainage ducts. After precisely locating the lymphatic channels and lymph node, all the lymph nodes that firstly receive lymphatic drainage are designated as trSLNs. We precisely distinguished the trSLNs, paSLNs and poSLNs. We found the average number of trSLNs ranged from1 to 6. In addition, we assessed the novel technique in a total of 125 breast cancer patients. trSLNs were successfully identified in all patients (detection rate: 100 %). The accuracy of trSLNs is 99.2%. Data from our study strongly suggest that our method is a feasible and effective for the detection of precise trSLNs in breast cancer with real-time observations. (ClinicalTrials.gov number, NCT02651142).

Radiotherapy of the lymphatic drainage pathways in breast carcinoma: time for a reassessment

Abstract Background The treatment administered for regional lymph nodes has altered dramatically in recent years. The state of the evidence on radiotherapy has also substantially improved and a reassessment is required. Materials and results Randomized studies are available on axillary surgery versus radiotherapy (AMAROS); on refraining from axillary dissection after a positive sentinel node (SN) when radiotherapy is planned (ACOSOG Z0011); and on adjuvant radiotherapy of the regional lymph nodes (LNs). ACOSOG Z0011 shows that refraining from axillary dissection is possible even when there are one or two positive SNs. The meta-analysis of the studies on adjuvant radiotherapy for the regional LNs (EORTC, Canadian, and French studies) shows a significant survival benefit with radiotherapy, and a Danish cohort study has confirmed this result. The reduction in breast cancer–specific mortality in these studies was partly based on a “systemic” effect of regional radiotherapy, with a reduction in the rate of distant metastases. Conclusions The principle applying in surgical treatment of the axilla is “less is not worse.” By contrast, the principle applying in radiotherapy of the regional lymph nodes is “more may be better in some circumstances.” There is as yet no clear explanation for the discrepancy between these two findings. An immunological effect (through immunogenic cell death due to irradiation) has been discussed. Further research is needed on which patients are today capable of benefiting from regional radiotherapy.

Central compartment management in patients with papillary thyroid cancer presenting with metastatic disease to the lateral neck: Anatomic pathways of lymphatic spread.

Papillary thyroid cancer (PTC) occasionally presents with metastases to the lateral neck, without clinically evident disease in the central neck. These cases may ultimately manifest as either skip metastases to the lateral compartment or as occult metastases in the central compartment. This is a retrospective review of 80 patients with PTC with metastases to the lateral cervical lymph nodes treated from 2006 to 2015. Photographs of the cadaveric dissections were used with permission from the author. Schematic illustrations were created to highlight lymphatic drainage pathways. The rate of skip metastasis in this cohort was 5%. Clinical evidence of central neck disease did not predict the pathologic status of the compartment. PTC rarely spreads to the lateral neck without depositing metastases within the central neck. This finding is supported by the anatomic pathways for lymphatic spread, not previously highlighted in the English literature. © 2017 Wiley Periodicals, Inc. Head Neck 39: 853-859, 2017.

Lymphatic Drainage to the Paravertebral Lymph Nodes in Breast Cancer Patients.

Aberrant, altered, or blocked lymphatic drainage may contribute to the high recurrence rate of breast cancer. Thus, an efficient evaluation of lymphatic drainage from the breasts and/or upper limbs is essential in the management of lymphedema and in ipsilateral primary or contralateral recurrent breast cancer patients. There are very few reports of lymphatic drainage to the paravertebral lymph nodes in patients with a lymphedema after breast cancer surgery with or without reconstruction. We used lymphoscintigraphy to examine lymphatic drainage in a case series. We observed five patients with upper limb and/or mammary lymphedema (after breast cancer surgery with or without reconstruction) who had lymphatic drainage from the upper limb or breast to the posterior intercostal and/or paravertebral lymph nodes. One patient also presented with nodal relapse at the time of our investigation. The cases from this study demonstrate the unusual, and mostly unrecognized, lymphatic drainage pathways toward lymph nodes, which may be at risk for further evolution of breast cancer.

Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumour response.

Our objective was to analyse the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. The study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1-T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumour administration of the radiopharmaceutical. Scintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumour response, both with the Miller-Payne system (non-detection 44.4%-detection 16.7%, p = 0.003) as well as the residual cancer burden (72.2%-28.6%, p<0.01). The scintigraphic detection of the sentinel node after intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumour response.

Selective sentinel node biopsy after intratumour administration of radiotracer in breast cancer patients treated with neoadjuvant chemotherapy in relation to the level of tumor response

PurposeOur objective was to analyze the accuracy of the sentinel node biopsy, taking into consideration the scintigraphy detection rate after the intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy. Materials and methodsThe study included 60 patients with a diagnosis of invasive breast carcinoma, stage T1–T3, who received treatment with neoadjuvant chemotherapy, and were subsequently subjected to breast surgery and sentinel node biopsy after intra-tumor administration of the radiopharmaceutical. ResultsScintigraphic detection of some sentinel node was achieved in 55/60 patients (91.6%). When those cases that received a second injection of the radiopharmaceutical, performed peri-areolarly due to a lack of tracer migration, were excluded, the detection rate dropped to 70% (42/60). When the detection of sentinel node, or its absence, was compared in those 42 patients, no differences were found with age, laterality-location of the lesion, size pre- and post-neoadjuvant chemotherapy, histological grade, or immunohistochemical profile. There were significant differences when comparing the groups according to the degree of pathological tumor response, both with the Miller–Payne system (non-detection 44.4%-detection 16.7%, p=0.003) as well as the residual cancer burden (72.2–28.6%, p<0.01). ConclusionsThe scintigraphic detection of the sentinel node after intratumoural administration of the radiopharmaceutical in patients with breast cancer who received neoadjuvant chemotherapy was below the optimal value, and sometimes a further, peri-areolar, injection was necessary, probably in relation to an alteration in the lymphatic drainage pathways. There was a significant inverse relationship between the detection of the sentinel node and level of pathological tumor response.

Patterns of lymph node metastasis identified following bilateral mandibular and medial retropharyngeal lymphadenectomy in 31 dogs with malignancies of the head.

Variable pathways of lymphatic drainage have been described in the dog head and neck. The aim of this study was to retrospectively assess the patterns of lymph node metastasis in dogs with malignancies of the head following bilateral mandibular and medial retropharyngeal lymphadenectomy. Thirty-one dogs were included. Median age at surgery was 10 years (range: 5 months to 14 years) and mean bodyweight was 21.4 ± 11.9 kg. Lymph node metastasis occurred in 14 dogs (45%), with spread to mandibular lymph nodes in 14 dogs and medial retropharyngeal metastasis in 11 dogs. Eight of 13 dogs (62%) with lymphatic metastasis and a lateralised lesion showed contralateral dissemination, while 12/13 (92%) showed ipsilateral metastasis. Of 13 dogs with oral malignant melanoma, four showed metastasis to all four lymph centres. Contralateral metastasis may occur in dogs with malignancies of the head and should be considered during staging and management.

F-18-FDG-avid lymph node metastasis along preferential lymphatic drainage pathways from the tumor-bearing lung lobe on F-18-FDG PET/CT in patients with non-small-cell lung cancer.

F-18-FDG-avid lymph node (LN) metastasis may preferentially occur along the lymphatic drainage pathway (LDP) from the tumor-bearing lobe in patients with non-small cell lung cancer (NSCLC) on FDG PET/CT. This study evaluated whether the identification of metastatic LNs according to LDP-based visual image interpretation can improve LN staging on FDG PET/CT in these patients. FDG PET/CT study was performed in 265 patients with NSCLC. The presence and LN station of metastatic LNs were determined by surgery or the clinical course. In the LDP-based interpretation, FDG-avid LNs, which were located along the preferential LDP from each tumor-bearing lobe and visually more intense in FDG uptake compared with the remaining LNs straying away from the preferential LDP, were diagnosed as metastatic. The result was compared with the quantitative method using a cutoff value of 2.5 for the maximum standardized uptake value. Of the total 1031 mediastinal and hilar LN stations with FDG-avid LNs in 265 patients, 179 stations in 66 patients were metastatic and the remaining 852 were benign. All the metastatic LN stations except for 2 stations showing skip metastasis were located along the main preferential LDP or another preferential LDP via a direct anatomic pathway from each tumor-bearing lung lobe. The specificity, accuracy, and PPV for identifying metastatic LN stations by LDP-based interpretation were 97.9, 95.7 and 89.5%, respectively, which were significantly greater compared with those of 92.7, 90.8 and 70.3% by the SUV-based method (P<0.001). The present study shows that FDG-avid LN metastasis preferentially occurs along the LDP from the tumor-bearing lobe in NSCLC patients. LDP-based visual image interpretation on FDG PET/CT can improve LN staging in these patients.

Obturator Canal Lymph Node Metastasis from Rectal Carcinoid Tumors: Total Mesorectal Excision May Be Insufficient

BackgroundOptimal surgical treatment for small early rectal carcinoids is controversial. Large tumors (greater than 2 cm) and those with imaging evidence of lymph node metastasis are generally treated by low anterior resection (LAR) with total mesorectal excision (TME). We first observed and reported that midgut carcinoid with extensive mesenteric lymphadenopathy often develops alternated lymphatic drainage pathways. We hypothesize that rectal carcinoids have the same potential to develop alternated lymphatic pathways outside the mesorectal envelope, which allows tumor deposits to be missed by traditional TME. MethodsTwenty-two consecutive rectal carcinoid surgical patient charts were reviewed to determine if alternated lymphatic drainage occurred and resulted in extra-mesorectal metastasis. We attempted to identify any risk factor(s) that may lead to developing such alternated lymphatic drainage pathways. ResultsThirteen patients underwent initial LAR with TME (13/22, 59 %) and nine underwent a staged debulking for locoregional residual disease or regional/distant metastasis after previous resection (9/22, 41 %). Fourteen (14/22, 64 %) underwent radio-guided surgery in attempt to achieve a higher level of pelvic/distant metastatic disease detection and debulking. Six patients (6/22, 27 %) had obturator canal lymph node metastases confirmed histologically. ConclusionsBased on our study, at least 27 % of rectal carcinoid patients may have extra-mesorectal metastasis that would be missed by the traditional TME. Radio-guided surgery can identify and remove such metastasis. The effect of having such extra-mesorectal metastasis and its surgical removal on long-term survival has yet to be determined.

A Simulation Model of Periarterial Clearance of Amyloid-β from the Brain

The accumulation of soluble and insoluble amyloid-β (Aβ) in the brain indicates failure of elimination of Aβ from the brain with age and Alzheimer's disease (AD). There is a variety of mechanisms for elimination of Aβ from the brain. They include the action of microglia and enzymes together with receptor-mediated absorption of Aβ into the blood and periarterial lymphatic drainage of Aβ. Although the brain possesses no conventional lymphatics, experimental studies have shown that fluid and solutes, such as Aβ, are eliminated from the brain along 100 nm wide basement membranes in the walls of cerebral capillaries and arteries. This lymphatic drainage pathway is reflected in the deposition of Aβ in the walls of human arteries with age and AD as cerebral amyloid angiopathy (CAA). Initially, Aβ diffuses through the extracellular spaces of gray matter in the brain and then enters basement membranes in capillaries and arteries to flow out of the brain. Although diffusion through the extracellular spaces of the brain has been well characterized, the exact mechanism whereby perivascular elimination of Aβ occurs has not been resolved. Here we use a computational model to describe the process of periarterial drainage in the context of diffusion in the brain, demonstrating that periarterial drainage along basement membranes is very rapid compared with diffusion. Our results are a validation of experimental data and are significant in the context of failure of periarterial drainage as a mechanism underlying the pathogenesis of AD as well as complications associated with its immunotherapy.

Intradermal microbubbles and contrast-enhanced ultrasound (CEUS) is a feasible approach for sentinel lymph node identification in early-stage breast cancer.

BackgroundMicrobubbles and contrast-enhanced ultrasound (CEUS) is a new technique for locating sentinel lymph node (SLN). The aim of this study is to explore the feasibility of SLNs tracing by CEUS using microbubbles in breast cancer patients and the value of enhancing patterns in diagnosing lymph nodes metastases.MethodsA clinical trial was registered (trial registration: ChiCTR-DDT-13003778). One hundred and one consecutive consenting patients with breast cancer undergoing SLN biopsy were enrolled. Before the surgery, microbubble was injected periareolarly. Lymphatic drainage pathway was detected by CEUS, and guidewire was deployed to locate the SLN before the operation. Blue dye was also used to help in tracing sentinel lymph node during the operation. The identification rate and the accuracy rate were recorded. Enhancing patterns of lymph nodes were recorded and compared with the pathological diagnosis.ResultsOf the 101 cases, SLNs in 99 cases were successfully identified by at least one tracer, including 98 cases identified by CEUS and 97 cases by blue dye. There was no significant difference between the two methods (P = 0.705). Guidewires were deployed successfully in all 98 cases, and the localized SLNs were all isolated successfully in the following operations. The status of SLNs isolated by CEUS was completely identical to that of the whole axillary lymph node while 7.1 % cases were misdiagnosed as negative by blue dye method. The sensitivity of predicting SLNs metastases by CEUS enhancing pattern was 81.8 %, the specificity was 86.2 %, and the positive and negative predictive values were 75.0 and 90.3 %, respectively.ConclusionsMicrobubbles and CEUS are feasible approaches for SLN identification. The enhancing patterns on CEUS may be helpful to recognize the metastasizing SLNs. This novel method may be a promising technique for the clinical application.

Understanding Lymphatic Drainage Pathways of the Ovaries to Predict Sites for Sentinel Nodes in Ovarian Cancer

In ovarian cancer, detection of sentinel nodes is an upcoming procedure. Perioperative determination of the patient's sentinel node(s) might prevent a radical lymphadenectomy and associated morbidity. It is essential to understand the lymphatic drainage pathways of the ovaries, which are surprisingly up till now poorly investigated, to predict the anatomical regions where sentinel nodes can be found. We aimed to describe the lymphatic drainage pathways of the human ovaries including their compartmental fascia borders. A series of 3 human female fetuses and tissues samples from 1 human cadaveric specimen were studied. Immunohistochemical analysis was performed on paraffin-embedded transverse sections (8 or 10 μm) using antibodies against Lyve-1, S100, and α-smooth muscle actin to identify the lymphatic endothelium, Schwann, and smooth muscle cells, respectively. Three-dimensional reconstructions were created. Two major and 1 minor lymphatic drainage pathways from the ovaries were detected. One pathway drained via the proper ligament of the ovaries (ovarian ligament) toward the lymph nodes in the obturator fossa and the internal iliac artery. Another pathway drained the ovaries via the suspensory ligament (infundibulopelvic ligament) toward the para-aortic and paracaval lymph nodes. A third minor pathway drained the ovaries via the round ligament to the inguinal lymph nodes. Lymph vessels draining the fallopian tube all followed the lymphatic drainage pathways of the ovaries. The lymphatic drainage pathways of the ovaries invariably run via the suspensory ligament (infundibulopelvic ligament) and the proper ligament of the ovaries (ovarian ligament), as well as through the round ligament of the uterus. Because ovarian cancer might spread lymphogenously via these routes, the sentinel node can be detected in the para-aortic and paracaval regions, obturator fossa and surrounding internal iliac arteries, and inguinal regions. These findings support the strategy of injecting tracers in both ovarian ligaments to identify sentinel nodes.

Quantification of molecular interactions between ApoE, amyloid-beta (Aβ) and laminin: Relevance to accumulation of Aβ in Alzheimer's disease

Accumulation of amyloid-β (Aβ) in plaques in the brain and in artery walls as cerebral amyloid angiopathy indicates a failure of elimination of Aβ from the brain with age and Alzheimer's disease. A major pathway for elimination of Aβ and other soluble metabolites from the brain is along basement membranes within the walls of cerebral arteries that represent the lymphatic drainage pathways for the brain. The motive force for the elimination of Aβ along this perivascular pathway appears to be the contrary (reflection) wave that follows the arterial pulse wave. Following injection into brain parenchyma, Aβ rapidly drains out of the brain along basement membranes in the walls of cerebral arteries; such drainage is impaired in apolipoprotein E ε4 (ApoE4) mice. For drainage of Aβ to occur in a direction contrary to the pulse wave, some form of attachment to basement membrane would be required to prevent reflux of Aβ back into the brain during the passage of the subsequent pulse wave. In this study, we show first that apolipoprotein E co-localizes with Aβ in basement membrane drainage pathways in the walls of arteries. Secondly, we show by Atomic Force Microscopy that attachment of ApoE4/Aβ complexes to basement membrane laminin is significantly weaker than ApoE3/Aβ complexes. These results suggest that perivascular elimination of ApoE4/Aβ complexes would be less efficient than with other isoforms of apolipoprotein E, thus endowing a higher risk for Alzheimer's disease. Therapeutic correction for ApoE4/Aβ/laminin interactions may increase the efficiency of elimination of Aβ in the prevention of Alzheimer's disease. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.

New findings and concepts on production and absorption of cerebrospinal fluid: reconsiderations and revisions of an unquestioningly accepted dogma of 100 years

It has been recently pointed out that there are fallacies in the bulk flow theory, a dogmatic idea of cerebrospinal fluid (CSF) physiology, which assumes that CSF is produced by the choroid plexus and circulates unidirectionally from the ventricles to the subarachnoid space to be absorbed by the arachnoid villi in the parietal region. Therefore, CSF physiology now needs to be reconsidered. Since there is free exchange of water between the CSF and the brain interstitial fluid (ISF), when considering the dynamics of water in the brain, we should regard these two fluid compartments collectively as brain extracellular fluid. In this review, I discuss the contentious issues in the traditional theory of CSF physiology, and then introduce new understandings of the production and absorption of the brain extracellular fluid, such as the capillary theory asserting that brain ISF is produced and absorbed mainly at the cerebral capillaries, the brain lymphatic drainage pathway, and the non-existence of unidirectional CSF circulation.

Testicular tumors: what radiologists need to know--differential diagnosis, staging, and management.

Cryptorchidism, family history, and infertility are risk factors for testicular cancer. Most testicular cancers occur in young men aged 18-35 years, and seminoma is the most common cell type. Testicular tumors are usually diagnosed at ultrasonography (US) and are staged at computed tomography (CT) or magnetic resonance (MR) imaging. At US, testicular tumors usually appear as a solid intratesticular mass. Because the differential diagnosis includes infarct and infection, correlation with patient history and symptoms is important. At staging CT or MR imaging, retroperitoneal lymph nodes are considered regional lymph nodes, and the greatest nodal diameter is used to distinguish among N1-N3 disease. The right testicular vein drains into the inferior vena cava, and the left testicular vein drains into the left renal vein. Because of venous and lymphatic drainage pathways, retroperitoneal lymph nodes are the initial landing station for testicular cancers. Enlarged lymph nodes in the supraclavicular region, chest, and pelvis are considered distant metastases. Testicular cancer is initially treated with orchiectomy. The patient may then undergo active surveillance, chemotherapy, radiation therapy, or retroperitoneal lymph node resection, depending primarily on the clinical stage. Radiologists play an important role in initial diagnosis, staging, and imaging surveillance of testicular malignancies.

White matter changes in dementia: role of impaired drainage of interstitial fluid.

White matter abnormalities on magnetic resonance imaging (MRI) are associated with dementia and include white matter hyperintensities (WMH; also termed leukoaraiosis) and visible perivascular spaces (PVS). We review the potential role of impaired drainage of interstitial fluid in the pathogenesis of WMH and PVS. Whereas the volume of extracellular space in the grey matter is tightly controlled, fluid accumulates and expands the extracellular spaces of the white matter in acute hydrocephalus, vasogenic edema and WMH. Although there are no conventional lymphatic vessels in the brain, there is very effective lymphatic drainage for fluid and solutes along restricted pathways in the basement membranes of cerebral capillaries and arteries in young individuals. Lymphatic drainage of the brain is impaired with age and in association with apolipoprotein E ε4, risk factors for Alzheimer's disease and cerebral amyloid angiopathy (CAA). Deposition of proteins in the lymphatic drainage pathways in the walls of cerebral arteries with age is recognized as protein elimination failure angiopathy (PEFA), as in CAA and cerebral autosomal dominant arteriopathy and leukoencephalopathy (CADASIL). Facilitating perivascular lymphatic drainage from the aging brain may play a significant role in the prevention of CAA, WMH and Alzheimer's disease and may enhance the efficacy of immunotherapy for Alzheimer's disease.

In vivo lymph node mapping by Cadmium Tellurium quantum dots in rats

BackgroundIntraoperative lymph node mapping (LNM) is highly significant for many surgeries in patients with cancer. Many types of tracers are currently used, but the ideal method has not yet been identified. We aimed to identify a stable lymphatic drainage pathway in an animal model and compared the effects of quantum dots (QD), a new fluorescent tracer, with those of methylene blue in intraoperative LNM. Materials and methodsIndian ink (0.2 mL) was subcutaneously injected into the plantar metatarsal regions of six Sprague–Dawley rats. After 2 wk of incubation and subsequent dissection, the potentially stained LNs were examined pathologically to identify the lymphatic drainage pathway. After applying anesthesia, 0.1 mL methylene blue (2%) and QD (1 mg/mL) were injected into the plantar metatarsal regions of six rats for intraoperative LNM. The QD group was observed with a near-infrared imaging system, and the methylene blue group was directly observed. Drainages were recorded at 5, 10, 30, 60, and 120 min and at 1 d. ResultsTwo three-level drainage pathways, that is, a peripheral drainage (popliteal LNs, inguinal LNs, and axillary LNs) and a central drainage (popliteal lymph node [LN], iliac LN, and renal LN) pathways were identified. Both methylene blue and QD stained the sentinel lymph node (SLNs) quickly, but methylene blue was difficult to identify in the deep tissues and the LNs beyond the SLN. Furthermore, the blue-stained LNs remain dyed for only 2 h. In contrast, the QDs exhibited high target-to-background ratios in both the SLNs and the following LNs. Additionally, the fluorescence lasted from 5 min–1 d after injection. ConclusionsAn ideal lymphatic drainage model was found. QDs are excellent tracers for intraoperative LNM compared with methylene blue. Near infrared fluorescent imaging is a promising LNM method for clinical practice.

Tracking the luminal exposure and lymphatic drainage pathways of intravaginal and intrarectal inocula used in nonhuman primate models of HIV transmission.

Over 80% of sexual HIV-1 transmissions originate from a single viral variant, but the underlying basis for this transmission bottleneck remains to be elucidated. Nonhuman primate models of mucosal virus transmission allow opportunities to gain insight into the basis of this mucosal bottleneck. We used simulated inocula consisting of either non-infectious vital dye or contrast dye with non-invasive magnetic resonance imaging (MRI) to visualize mucosal exposure and passive lymphatic drainage patterns following vaginal and rectal exposures in Indian origin rhesus macaques. Results revealed a limited overall distance of dye coverage from the anal verge following 1 ml (n = 8) intrarectally administered, which greatly increased with a 3 ml (n = 8) volume. Intravaginal dye exposure using 2 ml revealed complete coverage of the mucosa of the vagina and ectocervix, however dye was not detectable in the endocervix, uterus, fallopian tubes or ovaries in nuliparous sexually mature rhesus macaques (n = 9). In addition, following submucosal and intranodal injections of vital dye or MRI contrast dye in the rectum (n = 9), or distal and proximal vagina (n = 4), the lymphatic drainage pathways were identified as first the internal then common iliac chain followed by para-aortic lymph nodes. Drainage from the distal descending colon (n = 8) was via the para-colonic lymph nodes followed by the inferior mesenteric and para-aortic lymph nodes. Analysis after vaginal challenge with infectious SIVmac239 followed by euthanasia at day 3 revealed a pattern of viral dissemination consistent with the imaging results. These results provide insights into potential patterns of viral dissemination that can help guide efforts to better elucidate the earliest events of virus transmission and potential intervention strategies.