A Multicenter Global Registry of Paclitaxel Drug-Coated Balloon in Dysfunctional Arteriovenous Fistulae and Grafts: 6-Month Results.

PURPOSE: To assess the safety and clinical benefit of the Lutonix drug-coated balloon (DCB) catheter for the treatment of dysfunctional arteriovenous fistulae (AVF) and grafts (AVG) in a heterogenous real-world population. MATERIALS AND METHODS: This multicenter, prospective study enrolled 320 subjects from 12 countries in 25 sites across Europe and Asia. A total of 392 lesions were treated with the Lutonix 035 DCB catheter. Lesions were de novo and restenotic, located in every part of the circuit from the cannulation zone to central venous outflow. In-stent restenotic lesions also were treated. The primary safety endpoint was freedom from serious adverse events involving the access circuit through 30 days. The primary effectiveness endpoint was target lesion primary patency (TLPP) through 6 months. Secondary endpoints included access circuit primary patency (ACPP) at 6 months and the investigation of factors that would independently influence the primary endpoints. RESULTS: The primary safety endpoint was 95.5%, while TLPP was 73.9% at 6 months, per Kaplan-Meier survival analysis. ACPP was 71% at 6 months. TLPP for stenosis of AVFs was 78.1%. Subgroup analysis showed significantly improved TLPP when DCB was dilated for ≥120 seconds (P = .007). TLPP was significantly better when predilation occurred compared with cases where only DCB angioplasty was performed (77% vs 48.6%, P = .0005). CONCLUSIONS: The Lutonix AV Global Registry confirms that the Lutonix DCB is a safe and effective treatment option in real-world patients with dysfunctional AVF or AVG. Procedural details had a significant role in TLPP. No significant difference in TLPP was observed among different treatment areas.

Patterns of use, effectiveness and safety of gadolinium contrast agents: a European prospective cross-sectional multicentre observational study.

BACKGROUND: The EU gadolinium-based contrast agents (GBCA) market has changed in recent years due to the European Medicines Agency decision to suspend the marketing authorisation of linear GBCA and the marketing authorisation of new generic macrocyclic GBCA. The study aims to understand the patterns of (GBCA) use, and to study the effectiveness and safety of GBCA in routine practice across Europe. METHODS: Prospective, cross-sectional, multicentre, observational study in patients undergoing contrast-enhanced magnetic resonance. Reported usage patterns included indication, referral and examination details. Assessment of effectiveness included changes in radiological diagnosis, diagnostic confidence and image quality. Safety data were collected by spontaneous patient adverse event (AE) reporting. RESULTS: 2118 patients were included from 8 centres across 5 European countries between December 2018 and November 2019. Clariscan, Dotarem (gadoteric acid), Gadovist (gadobutrol) and ProHance (gadoteridol) were utilised in 1513 (71.4%), 356 (16.8%), 237 (11.2%) and 12 (0.6%) patients, respectively. Most were performed in CNS-related indications (46.2%). Mean GBCA doses were 0.10 mmol/kg body weight, except for Gadovist (mean 0.12 mmol/kg). GBCA use increased confidence in diagnosis in 96.2% of examinations and resulted in a change in radiological diagnosis in 73.9% of patients. Image quality was considered excellent or good in 96.1% of patients and across all GBCA. Four patients reported AEs (0.19%), with only 1 (0.05%) considered serious. CONCLUSIONS: This European study confirmed that GBCAs are used appropriately in Europe for a wide range of indications. The study demonstrated a significant increase in diagnostic confidence after GBCA use and confirmed the good safety profile of GBCAs, with comparable results for all agents used.

The multiple systemic artery to pulmonary artery fistulas resulting in severe irreversible pulmonary arterial hypertension in patient with previous history of pneumothorax.

BACKGROUND: Systemic artery to pulmonary artery fistulas (SA-PAFs), are extremely rare in people without congenital heart disease. In this group of patients pulmonary arterial hypertension was reported in the single case. Then, we describe a case of multiple SA-PAFs, which were the cause of severe nonreversible arterial pulmonary hypertension in a patient who had a right-sided pneumothorax 35 years earlier. CASE PRESENTATION: 52-year-old male Caucasian patient with echocardiographically confirmed pulmonary hypertension (PH) was admitted to cardiology department due to exertional dyspnea and signs of right ventricle failure. Routine screening for causes of secondary PH was negative. Right heart catheterization (RHC) confirmed a high degree arterial PH [mean pulmonary artery pressure (mPAP); 50,6 mmHg, pulmonary wedge pressure (PWP); 11,3 mmHg, pulmonary vascular resistance (PVR); 11,9 Wood's units (WU)] irreversible in the test with inhaled nitric oxide. Oxygen saturation (SaO2) of blood samples obtained during the first RHC ranged from 69.3 to 73.2%. Idiopathic pulmonary arterial hypertension was diagnosed. Treatment with inhaled iloprost and sildenafil was initiated. Control RHC, performed 5 months later showed values of mPAP (59,7 mmHg) and PVR (13,4 WU) higher in comparison to the initial measurement, SaO2 of blood obtained during RHC from upper lobe artery of the right lung was elevated and amounted 89.7%. Then, pulmonary arteriography was performed. Lack of contrast in the right upper lobe artery with the evidence of retrograde blood flow visible as a negative contrast in the right pulmonary artery was found. Afterwards, right subclavian artery arteriography detected a huge vascular malformation communicating with right upper lobe artery. Following computed tomography angiogram (angio-CT) additionally revealed the enlargement of bronchial arteries originated fistulas to pulmonary artery of right upper lobe. In spite of intensive pharmacological treatment, including the therapy of pulmonary hypertension and percutaneous embolisation of the fistulas, the patient's condition continued to deteriorate further. He died three months after embolisation due to severe heart failure complicated by pneumonia. CONCLUSION: Non-congenital SA-PAFs are extremely rare, however, they should be excluded in patients with pulmonary arterial hypertension and history of inflammatory or infectious disease of the lung and pleura, pneumothorax, cancer or Takayashu's disease and after chest trauma.

General technical remarks on 1HMRS translational research in 7T.

PURPOSE: The aim of the work was to share the practical experience of preclinical and clinical proton magnetic resonance spectroscopy (1HMRS) studies conducted using a 7-Tesla magnetic field strength scanner, taking into account the specificity of both settings in the context of translational research. MATERIAL AND METHODS: 1HMRS volunteer studies conducted using a Discovery 950 GE 7T scanner, were carried out with PRESS sequence, and a VOI measuring 2.0 × 2.0 × 2.0 cm3 placed in the white matter at the parietal occipital lobe. Rodent spectra obtained using a 7T Bruker were measured with PRESS, with a VOI 2.0 × 2.0 × 5.5 mm3 placed over the hippocampus. RESULTS: 1HMRS data from humans and rats show that the brain spectra obtained in the same field are characterised by a similar neurochemical structure and spectral resolution. Spectra obtained from rats demonstrate the following metabolites: NAA, Glu, Gln, Ins, Cho, Cr, PCr, Tau, GABA, Lac, NAAG, and Asp. In turn, spectra from humans allowed estimation of the following metabolites: Ala, NAA, Glu, Gln, Ins, Cho, Cr, PCr, Tau, GABA, Lac, NAAG, and Asp. Signals from Gln, Glu with chemical shift around 2.4 ppm, from Cr, PCr, and GABA at 3 ppm, and signals from Cho and Tau at approximately 3.2 ppm, can be properly separated and estimated both in humans and in rats. CONCLUSIONS: These results are promising in terms of broadening the knowledge of many neurological diseases by inducing them on animal models and then transferring this knowledge to clinical practice. In spite of this, important distinctions in the technical aspects and methodological differences of high-field 1HMRS in both preclinical and clinical conditions should be taken into account.

Chemical exchange saturation transfer (CEST) as a new method of signal obtainment in magnetic resonance molecular imaging in clinical and research practice.

The work describes the physical basis of the chemical exchange saturation transfer (CEST) technique; it presents the beginnings of the implementation of the method and its possible applications. The principles of correct data acquisition and possible solutions used during the design of the CEST sequence are shown. The main problems related to data analysis are indicated, and an example Z-spectrum from in vivo study of the rat brain is introduced. Furthermore, the parameters related to spectrum analyses such as magnetisation transfer asymmetry (MTRasym) and amide proton transfer asymmetry (APTasym) are presented. In the following part, different types of the CEST method often mentioned in the literature are discussed. Subsequently, the possible applications of the CEST method in both clinical and experimental practice are described.

Effectiveness, safety, and long-term outcomes of non-powered mechanical sheaths for transvenous lead extraction.

Aims: To analyse the effectiveness, safety and long-term outcomes of conventional non-powered mechanical systems for transvenous lead extraction (TLE) performed by experienced first operators. Outcomes were assessed according to lead location and type of operating room in which the procedure was performed. Methods and results: Data from 2049 patients (mean age: 65 years), with infectious (40%) or non-infectious (60%) indications, were analysed over a mean of 3.37 (±2.29) years. A total of 3426 leads were extracted; and, overall, 95% full procedural, 4% partial procedural, and 98% clinical success were demonstrated. Within the patient cohort, 1.8% (37/2049) experienced major complications, with cardiac tamponade being predominant (30/37). Cardiac tamponade was identified as the main cause of mortality, as well as the cause of all procedure-related deaths (6/2049; 0.3%). Cardiac tamponade occurred in 1.8% of atrial and 0.3% of right ventricular lead extractions, with fatal tamponade reported in 9% of atrial, 40% of ventricular, and 67% of coronary sinus lead extractions. No association between lead location and cardiac tamponade-related mortality was observed; however, lead location did affect the success of pericardiocentesis. The cardiac tamponade-related mortality rate was 37% when TLE was performed in an electrophysiology laboratory. No deaths were reported when the procedure was performed in a cardiac surgery or hybrid operating room. Long-term survival was improved when TLE was performed due to non-infectious indications, rather than pocket infection or lead-related endocarditis (P < 0.001). Conclusion: Using conventional non-powered mechanical sheaths, TLE was effective even in patients at high risk of complications.

Improvement in Quality of Life and Hemodynamics in Chronic Thromboembolic Pulmonary Hypertension Treated With Balloon Pulmonary Angioplasty.

BACKGROUND: The effect of balloon pulmonary angioplasty (BPA) on improvement in functional and hemodynamic parameters in chronic thromboembolic pulmonary hypertension (CTEPH) is known, but the quality of life (QoL) of patients treated with BPA has never been studied before.Methods and Results:Twenty-five patients with inoperable or persistent CTEPH were enrolled in the study and filled out the 36-item Short Form (SF-36v2) questionnaire twice: prior to commencement of BPA treatment and after ≥3 BPA sessions. In addition WHO functional class, distance on the 6-min walk test (6MWT) and hemodynamic parameters such as right atrial pressure (RAP), mean pulmonary artery pressure (mPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were assessed. QoL improved significantly in all domains, except for physical pain. Improvement in RAP (10.5±3.4 vs. 6.2±2.2 mmHg; P<0.05), mPAP (51.7±10.6 vs. 35.0±9.1 mmHg; P<0.05), CI (2.2±0.5 vs. 2.5±0.4 L/min·m2; P=0.04), PVR (10.4±3.9 vs. 5.5±2.2 Wood units; P<0.05), functional class (96% vs. 20% in WHO class III and IV, P<0.05) and improvement in 6MWT distance (323±135 vs. 410±109 m; P<0.05) was observed. The only significant correlation was between the mental component summary score of QoL after completion of treatment and percentage improvement in the 6MWT (-0.404, P<0.05). CONCLUSIONS: Alongside improvement in functional and hemodynamic parameters, BPA also provides significant improvement in QoL.

Cesarean scar pregnancy: uterine artery embolization combined with a hysterectomy at 13 weeks' gestation--a case report and review of the literature.

A cesarean scar pregnancy is a pregnancy located within the uterine muscle after previous cesarean sections. Recent years have shown a significant increase in the rate of CS and an improvement in the ultrasound diagnosis, and therefore a trend towards an increase in the rate of CSP cases has been reported in many countries. We report on a case of CSP diagnosed using ultrasound at 5/6 weeks'gestation and confirmedbymagnetic resonance imaging. The patient underwent surgical management at 13 weeks, combined with the chemioembolization of the uterine arteries. The current review aims to update the knowledge of the available treatment modalities.

Leads with the Cut Proximal Ends Migrated into the Heart and Vasculature: A Rare Phenomenon among 3847 Lead Extraction Procedures.

Background: The study aimed to describe the phenomenon of leads migrated (MPLE) into the cardiovascular system (CVS). Methods: Retrospective analysis of 3847 transvenous lead extractions (TLE). Results: Over a 17-year period, 72 (1.87%) MPLEs (median dwell time 137.5 months) were extracted, which included mainly ventricular leads (56.94%). Overall, 68.06% of MPLEs had their cut proximal ends in the venous system. Most of them were pacing (95.83%) and passive fixation (98.61%) leads. Independent risk factors for MPLE included abandoned leads (OR = 8.473; p < 0.001) and leads located on both sides of the chest (2.981; p = 0.045). The higher NYHA class lowered the probability of MPLE (OR = 0.380; p < 0.001). Procedure complexity was higher in the MPLE group (procedure duration, unexpected procedure difficulties, use of additional (advanced) tools and alternative venous approach). There were no more major complications in the MPLE group, but the rate of procedural success was lower due to more frequent retention of non-removable lead fragments. Extraction of MPLEs did not influence long-term survival. Conclusions: 1. Extraction of leads with MPLE is rare among other TLE procedures (1.9%), 2. risk factors include abandoned leads and presence of leads on both sides of the chest but a higher NYHA class lowers the probability of MPLE, 3. complexity of MPLE extraction is higher regarding procedure duration, unexpected procedure difficulties, use of advanced tools and techniques but rates of major complications are comparable, and 4. extraction of MPLEs did not influence long-term survival.

Endovascular embolization of varicoceles using n-butyl cyanoacrylate (NBCA) glue.

BACKGROUND: Varicoceles are abnormally dilated veins within the pampiniform plexus. They are caused by reflux of blood in the internal spermatic vein. The incidence of varicoceles is approximately 10-15% of the adolescent male population. The etiology of varicoceles is probably multifactorial. The diagnosis is based on Doppler US. Treatment could be endovascular or surgical. The aim of the study was to describe and evaluate a novel method of endovascular embolization of varicoceles using n-butyl cyanoacrylate (NBCA) glue. MATERIAL/METHODS: 17 patients were subjected to endovascular treatment of varicoceles using NBCA. A 2.8 Fr microcatheter and a 1:1 mixture of NBCA and lipiodol were used for embolization of the spermatic vein. RESULTS: All 17 procedures were successful. There were no complications. DISCUSSION: Embolization of varicoceles using NBCA glue is efficient and safe for all patients. The method should be considered as a method of choice in all patients. Phlebography and Valsalva maneuver are crucial for technical success and avoidance of complications. CONCLUSIONS: Endovascular treatment of varicoceles using NBCA glue is very effective and safe.

High Myopia and Thickness of Extraocular and Masticatory Muscles-7T MRI, Preliminary Study.

(1) Background: Myopia is one of the most common refractive errors in the world. The aim of this study was to evaluate the transverse dimensions of selected masticatory muscles (temporalis muscle and masseter muscle) versus the transverse dimensions of selected extraocular muscles (superior rectus, inferior rectus, medial rectus and lateral rectus) in emmetropic and high myopic subjects. (2) Methods: Twenty-seven individuals were included in the analysis, resulting in 24 eyeballs of patients with high myopia and 30 eyeballs of emmetropic subjects. A 7 Tesla resonance was used to analyze the described muscles. (3) Results: Statistical analysis showed differences in all analyzed extraocular muscles and all analyzed masticatory muscles between emmetropic subjects and high myopic subjects. In the high myopic subject group, statistical analysis showed four correlations. The three negative correlations were between the lateral rectus muscle and an axial length eyeball, refractive error and an axial length eyeball, and the inferior rectus muscle and visual acuity. The positive correlation was between the lateral rectus muscle and the medial rectus muscle. (4) Conclusions: The high myopic subjects are characterized by a larger cross-sectional area of extraocular muscles and masticatory muscles compared to the emmetropic subjects. Correlations were observed between the thickness of the extraocular muscles and the masticatory muscles. The lateral rectus muscle was related to the length of the eyeball. The phenomenon requires further study.

Comprehensive overview of the venous disorder known as pelvic congestion syndrome.

Pelvic venous disorders (PeVD) also known as Pelvic Congestion Syndrome (PCS) affect a great number of women worldwide and often remain undiagnosed. Gynecological symptoms caused by vascular background demand a holistic approach for appropriate diagnosis. This is a relevant cause of chronic pelvic pain and atypical varicose veins. The diagnosis is based on imaging studies and their correlation with clinical presentation. Although the aetiology of PCS still remains unclear, it may result from a combination of factors including genetic predisposition, anatomical abnormalities, hormonal factors, damage to the vein wall, valve dysfunction, reverse blood flow, hypertension and dilatation. The following paper describes an in-depth overview of anatomy, pathophysiology, symptoms, diagnosis and treatment of PCS. In recent years, minimally invasive interventions have become the method of first choice for the treatment of this condition. The efficacy of a percutaneous approach is high and it is rarely associated with serious complications.Key MessagesPelvic venous disorders demand a holistic approach for appropriate diagnosis.This article takes an in-depth look at existing therapies of Pelvic Congestion Syndrome and pathophysiology of this condition.Embolisation is an effective and safe treatment option.

Visual Tract Degradation in Bilateral Normal-Tension Glaucoma-Cortical Thickness Maps and Volumetric Study of Visual Pathway Areas.

The aim of the study was to evaluate changes in the central visual pathways during the early and advanced stages of bilateral normal-tension glaucoma (NTG). METHODS: The studied groups constituted patients with bilateral normal-tension glaucoma of the same stage (n = 45) and age-matched healthy volunteers (n = 17). All patients underwent ophthalmic examination and examination on a 1.5 Tesla Magnetic Resonance Scanner (Optima 360, GE Healthcare). Volume and cortical thickness analyses were performed using the open-source automated software package FreeSurfer. RESULTS: There was a significant difference in lateral geniculate nuclei volume between the control and advanced glaucoma groups in the right hemisphere (p = 0.03) and in the left hemisphere between the early and advanced glaucoma patients (p = 0.026). The optic chiasm volume differed significantly between the control and advanced NTG groups (p = 0.0003) and between early and advanced glaucoma patients (p = 0.004). Mean cortical thickness analysis revealed a significant increase in values in the advanced glaucoma group in the right Brodmann area 17 (BA17) (p = 0.007) and right BA18 (p = 0.049) as compared to early NTG. In the left BA18 area, the mean thickness of the cortex in the early glaucoma group was significantly lower than in the control group (p = 0.03). CONCLUSIONS: The increase in the grey matter thickness in the V1 region with more-advanced glaucoma stages may reflect compensatory hypertrophy. Additionally, the regions of the brain early affected during glaucoma with reduced thickness were the right lateral occipital gyrus and left lingual gyrus. The most prominent change during the course of glaucoma was the increase in grey matter thickness in the right cuneus.

Klippel-Trenaunay Syndrome: Employment of a New Endovascular Treatment Technique-Mechanochemical Ablation Using the Flebogrif System.

BACKGROUND: Klippel-Trenaunay syndrome (KTS) is characterized by a triad of symptoms; varicose veins and venous malformations (VMs), capillary malformations (port-wine stain), and soft tissue and bone hypertrophy. Herein, we retrospectively studied six patients with KTS who underwent treatment with the Flebogrif system and evaluated their outcomes. METHODS: Six KTS patients aged 16-22 years who had undergone 18 non-thermal ablations using the Flebogrif system were enrolled. All patients underwent multistage foam sclerotherapy with 3% polidocanol at 3-4-week intervals. RESULTS: Venous clinical severity score (VCSS) analysis showed improvement in the patients' clinical condition. All patients reported a significant improvement in aesthetic outcomes. One patient presented with recanalization of ablated marginal veins during the 24-month follow-up period. Patients could return to full activity within 7-10 days after the procedure. None of the patients experienced serious systemic complications. CONCLUSION: The use of the Flebogrif system in treating various forms of chronic venous insufficiency, including in patients with KTS, provides a high success rate with a high closure rate.

Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: a multicentre registry.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is a promising therapy for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are ineligible for pulmonary endarterectomy. AIMS: The present study aimed to evaluate the safety and efficacy of BPA for CTEPH using the first multicentre registry of a single European country. METHODS: Data were obtained from the Database of Pulmonary Hypertension in the Polish Population (NCT03959748), a prospective, multicentre registry of adult and paediatric pulmonary arterial hypertension (PAH) and CTEPH, for a total of 236 patients with confirmed CTEPH (124 women; mean age 67 years) who underwent 1,056 BPA procedures at eight institutions in Poland. RESULTS: In 156 patients who underwent follow-up assessments after a median of 5.9 (IQR: 3.0-8.0) months after final BPA, the mean pulmonary arterial pressure decreased from 45.1±10.7 to 30.2±10.2 mmHg (p<0.001) and pulmonary vascular resistance from 642±341 to 324±183 dynes (p<0.001), and the six-minute walking test (6MWT) improved from 341±129 to 423±136 m (p<0.001). Pulmonary injury related to the BPA procedure occurred in 6.4% of all sessions. Eighteen patients (7.6%) died during follow-up, including 4 (1.7%) who died within 30 days after BPA. Overall survival was 92.4% (95% confidence interval [CI]: 87.6%-94.9%) three years after the initial BPA procedure. CONCLUSIONS: This multicentre registry confirmed significant improvement of haemodynamic, functional, and biochemical parameters after BPA. Complication rates were low and overall survival comparable to the results of another registry. Therefore, BPA may be an important therapeutic option in patients with CTEPH in Poland.

Rapamycin Improves Recognition Memory and Normalizes Amino-Acids and Amines Levels in the Hippocampal Dentate Gyrus in Adult Rats Exposed to Ethanol during the Neonatal Period.

The mammalian target of rapamycin (mTOR), a serine/ threonine kinase, is implicated in synaptic plasticity by controlling protein synthesis. Research suggests that ethanol exposure during pregnancy alters the mTOR signaling pathway in the fetal hippocampus. Thus, we investigated the influence of pre-treatment with rapamycin, an mTORC1 inhibitor, on the development of recognition memory deficits in adult rats that were neonatally exposed to ethanol. In the study, male and female rat pups received ethanol (5 g/kg/day) by intragastric intubation at postanatal day (PND 4-9), an equivalent to the third trimester of human pregnancy. Rapamycin (3 and 10 mg/kg) was given intraperitoneally before every ethanol administration. Short- and long-term recognition memory was assessed in the novel object recognition (NOR) task in adult (PND 59/60) rats. Locomotor activity and anxiety-like behavior were also evaluated to exclude the influence of such behavior on the outcome of the memory task. Moreover, the effects of rapamycin pre-treatment during neonatal ethanol exposure on the content of amino-acids and amines essential for the proper development of cognitive function in the dentate gyrus (DG) of the hippocampus was evaluated using proton magnetic resonance spectroscopy (1H MRS) in male adult (PND 60) rats. Our results show the deleterious effect of ethanol given to neonatal rats on long-term recognition memory in adults. The effect was more pronounced in male rather than female rats. Rapamycin reversed this ethanol-induced memory impairment and normalized the levels of amino acids and amines in the DG. This suggests the involvement of mTORC1 in the deleterious effect of ethanol on the developing brain.

Quadrantanopia as the only symptom of post-COVID stroke in the occipital pole: Case report.

RATIONALE: This is a case report describing delayed complications of COVID-19 pneumonia, which evolved into the vascular-ischemic complications leading to quadrantanopia and MRI findings consistent with recent ischemic event in the occipital pole of the brain. PATIENT CONCERNS: We report a case of a 46-year-old woman with quadrantanopia due to stroke confirmed with brain MRI, secondary to COVID-19 infection with chronically elevated D-dimers and treated with anticoagulation/antithrombotic modalities. Quadrantanopia was the only symptom recognized by the patient of a stroke localized in the occipital pole of the brain. DIAGNOSIS: The patient was diagnosed with quadrantanopia due to stroke confirmed with brain MRI, secondary to COVID-19 infection. INTERVENTION: Patient underwent ophthalmological examination and MRI. OUTCOMES: A thrombotic or ischemic risks in the chronic recovery from COVID-19 should be considered in patients with elevated D-dimers. LESSONS: An MRI should be considered as a long term follow up for post-COVID-19 patients reporting ophthalmic or neurologic complains.

Saturation transfer MRI is sensitive to neurochemical changes in the rat brain due to chronic unpredictable mild stress.

Chemical exchange saturation transfer (CEST) MRI was performed for the evaluation of cerebral metabolic changes in a rat model of depressive-like disease induced by chronic unpredictable mild stress (CUMS). CEST Z-spectra were acquired on a 7 T MRI with two saturation B1 amplitudes (0.5 and 0.75 µT) to measure the magnetization transfer ratio (MTR), CEST and relayed nuclear Overhauser effect (rNOE). Cerebral cortex and hippocampus were examined in two groups of animals: healthy control (n = 10) and stressed (n = 14), the latter of which was exposed to eight weeks of the CUMS protocol. The stressed group Z-spectrum parameters, primarily MTRs, were significantly lower than in controls, at all selected frequency offsets (3.5, 3.0, 2.0, - 3.2, - 3.6 ppm) in the cortex (the largest difference of ~ 3.5% at - 3.6 ppm, p = 0.0005) and the hippocampus (MTRs measured with a B1 = 0.5 µT). The hippocampal rNOE contributions decreased significantly in the stressed brains. Glutamate concentration (assessed using ELISA) and MTR at 3 ppm correlated positively in both brain regions. GABA concentration also correlated positively with CEST contributions in both cerebral areas, while such correlation with MTR was positive in hippocampus, and nonsignificant in cortex. Results indicate that CEST is sensitive to neurometabolic changes following chronic stress exposure.

Insight into Glutamatergic Involvement in Rewarding Effects of Mephedrone in Rats: In Vivo and Ex Vivo Study.

Mephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.