The Ultra-Low-Profile Minos Endograft in Abdominal Aortic Aneurysms with Standard and Hostile Anatomy. A Multicenter Retrospective Study.

BACKGROUND: Narrow and tortuous iliac axes are the second most common reason the feasibility of endovascular aortic repair (EVAR), and low-profile endografts were conceived to overcome the limitation of narrow and tortuous iliac axes. This study aims to report the initial results of EVAR performed with the ultra-low-profile Minos® abdominal endograft through a retrospective study conducted across 3 high-volume centers. METHODS: We retrospectively reviewed a prospectively maintained database collecting all consecutive EVAR performed with the Minos endograft across 3 Centers of Vascular Surgery between 2020 and 2023. Patients' clinical and operative data, perioperative, and postoperative outcomes were recorded. RESULTS: Ninety patients received EVAR with the Minos endograft. Assisted technical success was 100%, with 6 unplanned adjunctive procedures. Two perioperative complications required reinterventions: 1 access site surgical bleeding and an iliac limb occlusion. All unplanned adjunctive procedures and early reinterventions (8 in 7 patients) occurred in abdominal aortic aneurysms with hostile iliac arteries or narrow carrefour. Over a mean follow-up of 14.2 ± 9.6 months, no deaths were observed, and all patients completed the scheduled surveillance protocol. Late reinterventions were 6 (6.7%): 2 type IA endoleaks (ELs), 1 type IB EL, 1 type II EL, and 2 limb occlusions. There was no significant difference in reintervention rates between aneurysms with hostile and standard anatomy. CONCLUSIONS: The Minos endograft is safe and effective in treating aneurysms with hostile and standard anatomy, and its results are maintained at a mean follow-up of 14 months. A larger sample size and a longer follow-up are necessary to assess the results on the longer term.

Five-Year Outcomes of Endovascular Aortic Repair With the TREO Abdominal Endograft.

PURPOSE: Newer generation abdominal endografts, including Treo (Terumo Aortic, Sunrise, Florida), have shown optimal safety and effectiveness in treating abdominal aortic aneurysms (AAAs), even with hostile anatomy over the short- and mid-term. The durability of such results, however, is still a controversial issue, due to the paucity of long-term data. Our aim is to show the long-term outcomes of endovascular aortic repair of both standard and hostile AAAs with the Treo endograft on a cohort of patients treated between 2016 and 2017. METHODS: We analyzed the postoperative follow-up of 37 consecutive patients who have undergone endovascular aortic repair (EVAR) with the Treo Endograft between 2016 and 2017, whose baseline clinical conditions, operative data, and short-term outcomes had been published in 2018. All patients were followed up by computed tomography angiography (CTA) at 6 and 12 months and 5 years postoperatively. Primary endpoints were aortic-related mortality, type I-III endoleak (EL), and reintervention rate. Secondary endpoints were the rates of type II ELs and aneurysm sac regression. RESULTS: Of 37 patients, 27 had at least one criterion of anatomic hostility and 11 were performed outside the device-specific instructions for use (IFU). In the perioperative period, we observed 100% technical success, with no perioperative mortality. Over a mean follow-up of 5.5 years (66 months), 3 patients (8.1%) were lost to follow-up and 3 (8.1%) died of non-aortic causes (overall survival: 91.9%). One type IA EL of an AAA with a hostile neck (but within the IFU) and a type III EL of an AAA with standard anatomy were observed and treated by endovascular relining (overall reintervention rate: 5.5%). Four type II ELs were associated with aneurysm sac stability over time and are still under surveillance. Mean aneurysm shrinkage was 11.25±8.30 mm. CONCLUSION: The optimal results of the Treo Endograft in terms of complication and reintervention rates reported over the mid-term by the current literature (ITA-ENDOBOOT registry) are maintained on the long term, both in case of hostile and friendly aortic anatomy, with a satisfactory shrinkage rate of the aneurysm sac. CLINICAL IMPACT: The innovative characteristics of Treo and its short-term results are well-known and reported. The present case series contributes to the scientific validation of a new-generation abdominal aortic endograft over the long-term, focusing especially on its performance in treating AAAs with hostile anatomy. Its 5-years outcomes confirm the optimal results already reported over the short- and mid-term.

Mini-Surgical Access Prevents Local Complications and Reduces Costs in Endovascular Aortic Repair.

BACKGROUND: This study aims to propose a minimally invasive surgical approach to the common femoral artery in endovascular aortic repair and assess its value by a single-center retrospective study including 118 patients. METHODS: Between 2017 and 2022, all patients receiving endovascular treatment for thoracic and abdominal aortic aneurysms in our center had the anterior wall of the common femoral artery exposed, through a 2-3 cm transverse groin incision, instead of a complete surgical cutdown. We access the artery with a purse-string suture, held tight with a tourniquet. After procedure completion, we tie the purse-string closing the arteriotomy. We retrospectively analyzed the cohort of all consecutive patients treated with endovascular aortic repair in this period and recorded primary and assisted technical success, operative time, in-hospital length of stay, access failure, and access-related complications, comparing the results with the current literature. RESULTS: All procedures were successful, with no perioperative mortality. Primary technical success was achieved in 116 patients; 2 required adjunctive procedures. No access failure or access-related complications (thrombosis, groin hematoma, lymphocele, wound dehiscence, or infection) occurred. Two accesses required conversion to complete femoral artery exposure and endarterectomy. Operatory time and length of in-hospital stay were comparable to the outcomes of the major studies reporting on percutaneous access, saving the costs of the closure devices. CONCLUSIONS: Minimally invasive surgical access is safe and feasible for endovascular aortic procedures. Compared to the costs of percutaneous access found in literature, it is cost-effective. It can be chosen whenever the percutaneous approach is not feasible or at a high risk of complications.

Emergent Endovascular Treatment of Thoracoabdominal Aortic Rupture in Behcet's Disease.

BACKGROUND: Aortic rupture in Behcet's disease is associated with high mortality rates. Endovascular approach with parallel graft technique can be a valid solution in emergency setting for the treatment of thoraco-abdominal aorta involvement in Behcet's disease. METHODS: We describe the clinical case of a 41-year-old man, urgently hospitalized for a rupture of thoraco-abdominal aorta with occlusion of the celiac trunk and involvement of superior mesenteric artery. The patient also presented a massive right hemothorax and a massive left pulmonary thromboembolism. An aortic endoprosthesis was deployed from the third bottom of the thoracic aorta to the origin of the renal arteries. Parallel stent-graft technique was used to preserve the patency of the superior mesenteric artery. The procedure was performed with local anaesthesia due to the critical conditions of the patient. The patient was discharged in good clinical conditions. RESULTS: The angio-computed tomography performed 6 months after surgery showed good deployment of the endoprosthesis and patency of the superior mesenteric artery. CONCLUSION: In high risk for surgery patients, endovascular treatment with parallel stent graft of thoraco-abdominal aorta rupture is safe and feasible.

In vivo tumor targeting and biodistribution evaluation of paramagnetic solid lipid nanoparticles for magnetic resonance imaging.

The current study was performed to evaluate the in vivo efficiency of a new nano-sized contrast agent called paramagnetic Solid Lipid Nanoparticles, pSLNs, having promising relaxivity properties for Magnetic Resonance Imaging application. Good stability and stealth properties toward macrophage uptake have been demonstrated. An in vivo MRI study resulted in an improved signal enhancement in the tumor tissue particularly when folate as targeting ligand was used to decorate the nanoparticles surface. Afterward, the biodistribution of pSLNs in several organs was investigated. The accumulation of pSLNs in kidneys, femoral bones, spleen and brain was quite low while high tropism of pSLNs was found for the liver. In this regard, approaches to improve the rate of the hepatic clearance have been proposed.

Robotic Surgery for Elective Repair of Visceral and Renal Artery Aneurysms: A Systematic Review.

Background: The treatment choice of visceral artery aneurysms in an elective setting is debated. The durability and the risk of reintervention with endovascular treatment are still reasons for concern, whereas open surgery is invasive and burdened by major complications. In anecdotal reports and isolated studies, robotic-assisted surgery seems to provide the possibility of a minimally invasive treatment and the durability of traditional open surgery, but the literature supporting this view is scarce. This review aims to collect the results of robotic-assisted surgery in the treatment of visceral artery aneurysms. Methods: A systematic search of the main research databases was performed: the study endpoints were mortality and conversion rates, perioperative morbidity, and freedom from late complications and reinterventions. Results: We identified 16 studies on 53 patients. All cases underwent successful resection, with three conversions to laparoscopy. Perioperative and aneurysm-related mortality were nil. Over a median follow-up of 9 months, two reinterventions were reported (3.6%). Conclusion: The robotic technique is safe and effective in treating splenic and renal artery aneurysms, and it should be considered as a valuable alternative to endovascular and open repair, although larger sample sizes and a longer-term follow-up are necessary to confirm such results.

Disappointing results of popliteal aneurysm endovascular treatment with a new self-expandable covered stent.

PURPOSE: To describe our clinical experience of endovascular exclusion of popliteal artery aneurysms using the new self-expandable covered stent SOLARIS® (Scitech Medical, Brazil), and to report its results in the context of surgical and endovascular treatment of popliteal artery aneurysms. CASE REPORT: Among 20 popliteal artery aneurysms undergoing open or endovascular repair in 2022 and 2023, two patients were successfully treated with the Solaris stentgraft. Both patients had a patent popliteal artery and three run-off vessels. After stentgraft implantation, they received dual antiplatelet therapy for three months and they were followed-up with Duplex scan and clinical evaluation after three months, and every six months thereafter. After three months, one Solaris stentgraft had complete thrombosis and the other ruptured, requiring surgical removal. No complications were observed among the other aneurysms treated with open repair or with the Viabahn® stentgraft. CONCLUSIONS: Endovascular treatment of popliteal aneurysms with the new covered self-expandable stent Solaris resulted in severe complications in the two cases reported, and in worse short-term outcomes than endovascular repair with Viabahn® and open repair. Its off-label use to treat popliteal artery aneurysms should be therefore discouraged.

Paramagnetic solid lipid nanoparticles as a novel platform for the development of molecular MRI probes.

Highly efficient magnetic resonance imaging (MRI) probes have been prepared by loading Gd(III) complexes on the surface of solid lipid nanoparticles (pSLNs). Applicability as molecular imaging probes is demonstrated by an in vitro model study with targeted pSLNs.

Endovascular and Open Surgical Treatment of Ruptured Splenic Artery Aneurysms: A Case Report and a Systematic Literature Review.

BACKGROUND: Ruptured splenic artery aneurysms (r-SAA), although rare, are burdened by high morbidity and mortality, even despite emergent surgical repair. It is suggested that endovascular treatment can achieve reduction in peri-operative death and complication rates, as in other vascular diseases, but evidence of such benefits is still lacking in this particular setting. We report a case of an r-SAA treated by trans-arterial embolization and then converted to open surgery for persistent bleeding, and we provide a systematic review of current results of open and endovascular repair of r-SAAs. MATERIALS AND METHODS: A 50-year-old male presenting in shock for a giant r-SAA underwent emergent coil embolization and recovered hemodynamic stability. On the following day, he underwent laparotomy for evacuation of the huge intraperitoneal hematoma, but residual bleeding was noted from the splenic artery, which was ligated after coil removal, and a splenectomy was performed. A systematic literature review of the reported mortality and complications of r-SAA undergoing open (OSR) or endovascular (EVT) treatment was performed using the main search databases. All primary examples of research published since 1990 were included regardless of sample size. The main outcome measures were mortality and reinterventions. Secondary outcomes were post-operative complications. RESULTS: We selected 129 studies reporting on 350 patients-185 treated with OSR and 165 with EVT. Hemodynamically unstable patients and ruptures during pregnancy were more frequently treated with open repair. Overall, there were 37 deaths (mortality: 10.6%)-24 in the OSR group and 13 in the EVTr group (mortality: 12.9% and 7.8% respectively, p-value: 0.84). There were 37 reinterventions after failed or complicated endovascular repair -6 treated with endovascular re-embolization and 31 with laparotomy and splenectomy (22.4%); there were 3 (1.6%) reinterventions after open repair. Overall complication rates were 7.3% in the EVT group (n: 12) and 4.2% in the OSR group (n: 7), and did not require reintervention. No significant differences in overall complications or in any specific complication rate were observed between the two groups. CONCLUSIONS: Current results of r-SAA treatment show equipoise terms of morbidity and mortality between open and endovascular repair; however, in case of hemodynamic instability and rupture during pregnancy, open surgery might still be safer. Moreover, endovascular repair is still burdened by a significantly higher rate of reinterventions, mostly with conversions to open surgery.

Sensing Technologies for Extravasation Detection: A Review.

Peripheral intravenous catheters are administered for various purposes, such as blood sampling or the infusion of contrast agents and drugs. Extravasation happens when the catheter is unintentionally directed outside of the vein due to movement of the intravascular catheter, enhanced vascular permeability, or occlusion of the upstream vein. In this article, extravasation and its mechanism are discussed. Subsequently, the sensorized devices (e.g., single sensor and multimodal detection) to identify the extravasation phenomena are highlighted. In this review article, we have shed light on both physiological and engineering points of view of extravasation and its detection approaches. This review provides an overview on the most recent and relevant technologies that can help in the early detection of extravasation.

Spinal cord ischemia complicating treatment of abdominal aortic aneurysms: a legal overview.

BACKGROUND AND AIM: Spinal cord ischemia following open or endovascular aneurysm repair of the abdominal aorta is rare but highly disabling complication. The aim of this work is to report on its occurrence and its legal consequences. METHODS: We report a case of spinal cord ischemia complicating an endovascular aortic repair, its management and sequalae, comparing it with the existing literature and we examine its legal consequences resulting in a malpractice lawsuit and the final decision of the judge. RESULTS: Although the causal relation between SCI and the neurological deficits reported were assessed by the Court, no element of responsibility imputable to the Hospital or the Medical Staff were found, since the defendant had made every effort to prevent it in the preoperatory setting, and to treat it once it established in the post-operative phase. CONCLUSIONS: predictable but unpreventable complications of necessary interventions rule out medical malpractice, as long as the patient is fully informed about the risks and benefits of the treatment, and provided that in the perioperative setting all due measures are taken in order to prevent it and treat it.

Human cord blood CD34+ progenitor cells acquire functional cardiac properties through a cell fusion process.

The efficacy of cardiac repair by stem cell administration relies on a successful functional integration of injected cells into the host myocardium. Safety concerns have been raised about the possibility that stem cells may induce foci of arrhythmia in the ischemic myocardium. In a previous work (36), we showed that human cord blood CD34(+) cells, when cocultured on neonatal mouse cardiomyocytes, exhibit excitation-contraction coupling features similar to those of cardiomyocytes, even though no human genes were upregulated. The aims of the present work are to investigate whether human CD34(+) cells, isolated after 1 wk of coculture with neonatal ventricular myocytes, possess molecular and functional properties of cardiomyocytes and to discriminate, using a reporter gene system, whether cardiac differentiation derives from a (trans)differentiation or a cell fusion process. Umbilical cord blood CD34(+) cells were isolated by a magnetic cell sorting method, transduced with a lentiviral vector carrying the enhanced green fluorescent protein (EGFP) gene, and seeded onto primary cultures of spontaneously beating rat neonatal cardiomyocytes. Cocultured EGFP(+)/CD34(+)-derived cells were analyzed for their electrophysiological features at different time points. After 1 wk in coculture, EGFP(+) cells, in contact with cardiomyocytes, were spontaneously contracting and had a maximum diastolic potential (MDP) of -53.1 mV, while those that remained isolated from the surrounding myocytes did not contract and had a depolarized resting potential of -11.4 mV. Cells were then resuspended and cultured at low density to identify EGFP(+) progenitor cell derivatives. Under these conditions, we observed single EGFP(+) beating cells that had acquired an hyperpolarization-activated current typical of neonatal cardiomyocytes (EGFP(+) cells, -2.24 ± 0.89 pA/pF; myocytes, -1.99 ± 0.63 pA/pF, at -125 mV). To discriminate between cell autonomous differentiation and fusion, EGFP(+)/CD34(+) cells were cocultured with cardiac myocytes infected with a red fluorescence protein-lentiviral vector; under these conditions we found that 100% of EGFP(+) cells were also red fluorescent protein positive, suggesting cell fusion as the mechanism by which cardiac functional features are acquired.

Is open repair still the gold standard in visceral artery aneurysm management?

BACKGROUND: Visceral artery aneurysms and pseudoaneurysms represent a rare disease with high mortality. The aim of this study was to report a single center experience of open repair (OR) and endovascular treatment (ET) of 94 patients, and to analyze short- and midterm results. METHODS: Between 1988 and 2010, 94 patients, 43 men and 51 women, mean age of 57.6 years (range, 23-87 years), were referred to our Institute with a diagnosis of visceral artery aneurysm or pseudoaneurysm. Arteries involved were splenic artery in 44 cases, hepatic artery in 17, renal artery in 18, superior mesenteric artery in six, celiac trunk in three, gastroduodenal in two, and pancreaticoduodenal in four. An abdominal aortic aneurysm coexisted in three (3%) cases, whereas in six (6%) cases, there were multiple visceral aneurysms. ET was indicated based on the anatomical location of the aneurysm or for patients at high risk for surgery. RESULTS: A total of 74 patients underwent OR, whereas ET was performed in 20 patients. Technical success was achieved in all cases treated by open surgery. Splenectomy was performed in 11 cases, and in six, splenic autotransplantation was performed. At 6 months of follow-up, a Tc99m-labeled red cell scintigraphy showed that autotransplants were viable in four patients (67%). No cases of pancreatitis or splenic infarction were observed. Among renal artery aneurysms, nephrectomy was necessary in one case of renal infarction for massive thrombosis of the ex-vivo reconstructed renal artery. Four surgical conversions were recorded (one thrombosis of the hepatic artery, one massive hemorrhage after embolization of superior mesenteric artery aneurysm, and two cases of sac enlargement after 24 and 48 months). An endoleak was present in a patient treated for a splenic artery aneurysm, but it resolved spontaneously after 6 months. No complications were observed in patients undergoing surgical conversion after ET. Perioperative mortality in the surgical group was 1.3% (1/74). There was no perioperative mortality in the endovascular group. No statistically significant difference was found between groups in terms of perioperative mortality (p = 1.00). Perioperative morbidity was 9.4% (7/74) in the surgical group, and 10% (2/20) in the endovascular group (p = 1.00). Follow-up was available for 16 patients in the endovascular group (80%) and 63 in the surgical group (85%), with a mean duration of 42 months (1-192 months). In the whole cohort, actuarial survival at 10 years was 68%. The Kaplan-Meier estimates of survival at 1 and 5 years were 100% and 85%, respectively, for OR, and 100% and 40%, respectively, for ET, with no significant difference between the two groups CONCLUSION: ET is safe and feasible in selected patients, but incomplete exclusion may be observed, requiring late surgical conversion in a significant number of patients. Long-term results (high survival, low complication rate) confirm the durability of the surgical approach that in our experience remains the gold standard with satisfactory results, especially for aneurysms involving the visceral hilum.

An ultrasound-guided injection method for a syngeneic orthotopic murine model of breast cancer.

Breast cancer is the most common cancer among women worldwide. For high-risk women, contrast enhanced (CE)-magnetic resonance imaging (MRI) is recommended as supplemental screening together with mammography. The development of new MRI contrast agents is an active field of research, which requires efficacy tests on appropriate preclinical pathological models. In this work, a refined method to orthotopically induce breast cancer in BALB/c mice was developed using ultrasound (US) as a guide for the precise localisation of the tumour induction site and to improve animal welfare. The method was coupled with CE-MRI to characterise the evolution of the tumoural lesion.

Mesoangioblasts from ventricular vessels can differentiate in vitro into cardiac myocytes with sinoatrial-like properties.

Cardiac mesoangioblasts (MABs) are a class of vessel-associated clonogenic, self-renewing progenitor cells, recently identified in the post-natal murine heart and committed to cardiac differentiation. Cardiomyocytes generated during cardiogenesis from progenitor cells acquire several distinct phenotypes, corresponding to different functional properties in diverse structures of the adult heart. Given the special functional relevance to rhythm generation and rate control of sinoatrial cells, and in view of their prospective use in therapeutical applications, we sought to determine if, and to what extent, cardiac mesoangioblasts could also differentiate into myocytes with properties typical of mature pacemaker myocytes. We report here that a subpopulation of cardiac mesoangioblasts, induced to differentiate in vitro into cardiomyocytes, do acquire a phenotype with specific mature pacemaker myocytes properties. These include expression of the HCN4 isoform of pacemaker ("funny", f-) channels and connexin 45 (Cx45), as well as reduced expression of inwardly-rectifying potassium channels. Furthermore, MAB-derived myocytes form agglomerates of pacing cells displaying stable rhythmic activity, and as in native cardiac pacemaker cells, f-channel modulation by autonomic transmitters contributes to control of spontaneous rate in differentiated mesoangioblasts. These data represent the first evidence for in vitro generation of pacemaker-like myocytes from proliferating non-embryonic stem/progenitor cells.

Fluorescence-guided surgery using indocyanine green in dogs with superficial solid tumours.

BACKGROUND: Near-infrared fluorescence (NIRF) imaging is a relatively novel technique that can aid surgeons during intraoperative tumour identification. METHODS: Nine canine oncology patients (five mammary gland tumours, three mast cell tumours and one melanoma) received intravenous indocyanine green (ICG). After 24 hours, tumours were resected and fluorescence intensities of tumours and surroundings were evaluated. Additional wound bed tissue was resected if residual fluorescence was present after tumour resection. Ex vivo, fluorescence-guided dissection was performed to separate tumour from surrounding tissue. RESULTS: Intraoperative NIRF-guided tumour delineation was feasible in four out of nine dogs. Wound bed imaging after tumour removal identified nine additional fluorescent lesions, of which four contained tumour tissue. One of these four true positive in vivo lesions was missed by standard-of-care inspection. Ex vivo fluorescence-guided tumour dissection showed a sensitivity of 72 per cent and a specificity of 80 per cent in discriminating between tumour and surrounding tissue. CONCLUSION: The value of ICG for intraoperative tumour delineation seems more limited than originally thought. Although NIRF imaging using ICG did identify remaining tumour tissue in the wound bed, a high false positive rate was also observed.

Preliminary safety and imaging efficacy of the near-infrared fluorescent contrast agent DA364 during fluorescence-guided surgery in dogs with spontaneous superficial tumors.

Tumor-targeting contrast agents may facilitate resection of solid neoplasms during fluorescence-guided surgery. Preliminary safety and imaging efficacy of the near-infrared fluorescent probe DA364 were evaluated during surgical resection of spontaneous solid tumors in 24 dogs. Intra-operative imaging was performed in situ and on excised specimens to evaluate fluorescence intensities of tumor and adjacent tissues. After standard-of-care tumor resection, the wound bed was imaged again, and additional tissue was excised if residual fluorescence was detected. DA364 was well tolerated after intravenous administration. The median tumor-to-background ratio in situ for mammary tumors, mast cell tumors and sarcomas was 1.8 (range 1.2-3.9), 2.2 (range 1.0-5.6), and 4.2 (range 2.0-4.3), respectively. Qualitative intra-operative tumor identification was feasible in half of the cases. Remaining fluorescence was detected in four wound beds that contained residual disease, and in11 tumor-free wound beds, confirmed by histopathology. Overall, DA364 did not raise safety concerns and showed accumulation in different types of spontaneous tumors, showing potential to pinpoint residual disease. Larger clinical trials are necessary to select accurate dosing and imaging protocols for specific indications to evaluate the sensitivity and specificity of the agent.

Distribution of the pacemaker HCN4 channel mRNA and protein in the rabbit sinoatrial node.

Several studies of the pacemaker mechanisms in mammalian cells, most of which were carried out in cells isolated from the rabbit sinoatrial node (SAN), have highlighted the role of the I(f) current. While the distribution of Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels, the molecular correlates of f-channels, is known at the mRNA level, the identification of f-channel proteins in this tissue is still undetermined. Here we investigate HCN protein expression in the rabbit pacemaker region. We found that HCN4 is the main isoform, and set therefore to analyze its distribution within the SAN and surrounding areas with the aim of correlating protein expression and pacemaking function. The analysis was carried out in tissue slices and single cells of the intercaval area, which includes the crista terminalis (CT), the SAN, and the septum interatrialis (SI). Immunolabeling, in situ hybridization, qRT-PCR analysis, and electrophysiological recordings identified the SAN as a region characterized by high HCN4 signal and current levels, while the expression in the CT and in the SI was either negligible or absent. Detailed analysis of the central SAN area showed that cells are predominantly distributed in islets interconnected by cell prolongations, and single-cell HCN4 labeling suggested sites of channel clustering. Our data indicate that in the rabbit SAN, HCN4 proteins are major constituents of native f-channels, and their distribution matches closely the SAN as defined morphologically and electrophysiologically. Until recently, the SAN was identified as the region where Cx43 and atrial natriuretic peptide are not expressed; we propose here that expression of HCN4 is an appropriate tool to map and identify the cardiac SAN pacemaker region.

Environment-specific spectral modeling: A new tool for the analysis of biological specimens.

The recent discovery of fluorescent dyes for improving pathologic tissues identification has highlighted the need of robust methods for performance validation especially in the field of fluorescence-guided surgery. Optical imaging of excised tissue samples is the reference tool to validate the association between dyes localization and the underlying histology in a controlled environment. Spectral unmixing may improve the validation process discriminating dye from endogenous signal. Here, an innovative spectral modeling approach that weights the spectral shifts associated with changes in chemical environment is described. The method is robust against spectral shift variations and its application leads to unbiased spectral weights estimates as demonstrated by numerical simulations. Finally, spectral shifts values computed pixel-wise from spectral images are used to display additional information with potential diagnostic value.