MRI Monitoring Research Articles

PH-Responsive nanocomposite fibres allowing MRI monitoring of drug release.

Magnetic resonance imaging (MRI) is one of the most widely-used non-invasive clinical imaging tools, producing detailed anatomical images whilst avoiding side effects such as trauma or X-ray radiation exposure. In this article, a new approach to non-invasive monitoring of drug release from a delivery vehicle via MRI was developed, using pH-responsive Eudragit L100 and S100 fibres encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) and carmofur (a drug used in the treatment of colon cancer). Fibres were prepared by electrospinning, and found to be smooth and cylindrical with diameters of 645 ± 225 nm for L100 and 454 ± 133 nm for S100. The fibres exhibited pH responsive dissolution behaviour. Around the physiological pH range, clear pH-responsive proton relaxation rate changes due to matrix swelling/dissolution can be observed: r2 values of L100 fibres increase from 29.3 ± 8.3 to 69.8 ± 2.5 mM-1 s-1 over 3 h immersion in a pH 7.4 medium, and from 13.5 ± 2.0 mM-1 s-1 to 42.1 ± 3.0 mM-1 s-1 at pH 6.5. The r2 values of S100 fibres grow from 30.4 ± 4.4 to 64.7 ± 1.0 mM-1 s-1 at pH 7.4, but at pH 6.5, where the S100 fibres are not soluble, r2 remains very low (< 4 mM-1 s-1). These dramatic changes in relaxivity demonstrate that pH-responsive dissolution results in SPION release. In vitro drug release studies showed the formulations gave rapid release of carmofur at physiological pH values (pH 6.5 and 7.4), and acid stability studies revealed that they can protect the SPIONs from digestion in acid environments, giving the fibres potential for oral administration. Exploration of the relationship between relaxivity and carmofur release suggests a linear correlation (R2 > 0.94) between the two. Mathematical equations were developed to predict carmofur release in vitro, with very similar experimental and predicted release profiles obtained. Therefore, the formulations developed herein have the potential to be used for non-invasive monitoring of drug release in vivo, and could ultimately result in dramatic reductions to off-target side effects from interventions such as chemotherapy.

MRI monitoring of sea spray freezing.

Sea spray icing is a common hazard for vessels and offshore structures in cold climates. In this paper, quantitative 3D MRI and T1-T2 mapping of the formation of sea spray ice were performed. Three different freezing regimes were employed. During freezing, changes in both relaxation times and signal intensity were greater than an order of magnitude. Results show strong differences in brine intensity and distribution for the three freezing regimes. The observed ranges of spin densities and relaxation times during freezing are well suited to measurements with portable NMR devices. There is a considerable potential for the use of MRI in studies of sea spray ice.

ACTR-19. REPORT ON THE COMBINATION OF AXITINIB AND TUMOR TREATING FIELDS (TTFIELDS) IN THREE PATIENTS WITH RECURRENT GLIOBLASTOMA

Abstract OBJECTIVE Tumor Treating Fields (TTFields) significantly improved survival of newly diagnosed glioblastoma (ndGBM) patients in the EF-14 trial. Axitinib is an orally available tyrosine kinase inhibitor which is approved for the treatment of metastatic renal cell carcinoma. It has a high affinity and specificity for vascular endothelial growth factor receptors. In phase 2 trials, Axitinib improved response rate and PFS in recurrent GBM (rGBM) patients with a manageable toxicity profile. Here, three rGBM patients treated with TTFields and Axitinib (AxiTTFields) are presented. PATIENT SECTION A 53-year-old male patient (#1) presented with a progressing GBM after initial surgery, radiochemotherapy followed by 4 cycles of temozolomide (TMZ) and TTFields. In a 46-year-old male patient (#2), early progress occurred after surgery, radiochemotherapy and 3 cycles of TMZ combined with TTFields. In both patients Axitinib was added to the treatment regimen to meet the urgent need of an alternative treatment. In a 61-year-old male patient (#3) with rGBM after surgery, radiochemotherapy and 6 cycles of TMZ, TTFields therapy was initiated at recurrence and the treatment regimen was adapted to AxiTTFields. RESULTS No additional adverse events due to the combined therapy of AxiTTFields were observed. Patients #1 and #2 were on AxiTTFields therapy for more than 8 months, presenting an improved neurological status with a partial response in the MRI 3 months after initiating AxiTTFields. #3 declined in his neurological status without any change in the MRI monitoring and died 2.4 months after initiating AxiTTFields. With an average of 77%, the TTFields usage rate was above the independent prognostic threshold of 75%, underlining the feasibility of this approach. CONCLUSION AxiTTFields was feasible and safe in three rGBM patients. The addition of Axitinib to TTFields therapy is a promising approach and safety/feasibility will be further investigated in a pilot trial.

SURG-30. CLINICAL COURSE OF IDH-MUTATED LOW-GRADE GLIOMAS DURING THE POSTSURGICAL ACTIVE MONITORING PHASE: ASYMPTOMATIC PATIENTS, WELL CONTROLLED SEIZURES, BUT CONTINUOUS GROWTH OF TUMOR RESIDUES

Abstract INTRODUCTION Postponing adjuvant treatment after resection in IDH-mutated low-grade glioma (LGG) seems appropriate in selected patients. Here we describe the clinical course of these patients during post-resection active monitoring with MRI scans, as literature on this topic is scarce. METHODS We included IDH-mutated LGG patients that underwent surgery between 2003–2016, with clinical follow-up including MR scans available. Samples were classified according to the 2016 WHO classification. We collected baseline clinical information, estimates of seizure control during follow-up, longitudinal evolution of post-resection LGG volumes when adjuvant therapy was postponed, and the clinicians’ reasons to either start immediate adjuvant treatment or postpone treatment, and reasons to initiate adjuvant treatment in later stage. We compared patients that underwent immediate postsurgical adjuvant treatment with patients that underwent active MRI monitoring until further progression. RESULTS AND CONCLUSIONS 197 patients were included, of which 108 were IDH-mutated astrocytomas, and 89 were oligodendrogliomas. Of these, 97 patients were actively followed with MRI scans, and 100 patients underwent immediate adjuvant therapy after initial surgery. Patients that received immediate adjuvant therapy were older and had less extensive resections than patients wherein adjuvant treatment was postponed (median age 45 years vs. 37 years, P&lt; 0.001; median postoperative tumor volume 31cm3 vs 2.68cm3, P&lt; 0.001). The duration of the active surveillance period in the patients wherein adjuvant treatment was postponed correlated with the extent of resection, with shorter time until adjuvant treatment in case of larger postoperative tumor volumes. All LGG lesions showed continuous growth during the active surveillance period, with median growth rates of 3mm/year for oligodendrogliomas and 4mm/year in IDH- mutated astrocytomas (P = 0.0093). Seizures were well controlled, with the majority of patients using only one anti-epileptic drug. The majority of patients stayed asymptomatic during follow-up, and the reason to initiate further adjuvant treatment was always radiological growth.

Clinical FDG-PET Findings in Patients with Temporal Lobe Epilepsy: Concordance with EEG and MRI.

We aimed to study the yield of PET in temporal lobe epilepsy (TLE) by analyzing the correlation of PET findings with MRI, and interictal and ictal EEG findings, in a single-center cohort of patients with TLE. Predictors of PET thalamic changes and its role in predicting postsurgical outcome were also studied. This was a retrospective study of 39 patients with TLE who underwent MRI, PET, and scalp video EEG monitoring at the University at Buffalo, New York from 2001 to 2011 during presurgical evaluation. PET-defined metabolism of the temporal lobes was evaluated using a 4-point ordinal rating scale. PET hypometabolism was associated with a variation in ictal (P = .034) and interictal (P<.001) foci in both lesional (by MRI) and nonlesional patients. Nonlesional MRI scans were associated with none to mild temporal PET hypometabolism (71% of patients) while lesional MRI scans were associated with moderate to severe hypometabolism (82% of patients) (P = .006). The odds of thalamic hypometabolism were 5.36 times higher when there was moderate to severe temporal hypometabolism (P = .039). This study underscores the utility of PET in localizing ictal foci in TLE patients even in those with normal MRI. The degree of PET hypometabolism corresponds to presence of MRI pathology. Coexistent thalamic hypometabolism with temporal hypometabolism suggests a secondary effect of distant temporal network disruption. Extratemporal metabolism is a predictor of poor postsurgical seizure outcome in TLE patients.

Treatment outcomes in patients with pyogenic vertebral osteomyelitis who have cirrhosis

Early diagnosis and proper treatment of pyogenic vertebral osteomyelitis (PVO) in patients with cirrhosis is challenging to clinicians, and the mortality rate is expected to be high. A retrospective study was conducted to investigate the treatment outcome in PVO patients with cirrhosis and to identify the predictors of their mortality. Mortality was divided into two categories, 30-day and 90-day mortality. A stepwise multivariate logistic regression model was used to identify predictors of mortality. Eighty-five patients were identified after initial exclusion. The patients’ mean age was 60.5 years, and 50 patients were male. The early mortality rates within 30 and 90 days were 17.6% and 36.5%, respectively. Multivariate analysis revealed that increased age, CTP class C, and bacteremia at the time of PVO diagnosis were predictors of 30-day mortality, while higher MELD score, presence of combined infection, and multiple spinal lesions were predictors of 90-day mortality. Attention should be paid to the high mortality between 30 and 90 days after PVO diagnosis (18.8%), which was higher than the 30-day mortality. Liver function was consistently a strong predictor of mortality in PVO patients with cirrhosis. The high-risk patients should be targeted for an aggressive diagnostic approach, using spinal MRI and intensive monitoring and treatment strategies.

MRI monitoring of temperature and displacement for transcranial focus ultrasound applications

BackgroundTranscranial focus ultrasound applications applied under MRI-guidance benefit from unrivaled monitoring capabilities, allowing the recording of real-time anatomical information and biomarkers like the temperature rise and/or displacement induced by the acoustic radiation force. Having both of these measurements could allow for better targeting of brain structures, with improved therapy monitoring and safety. MethodWe investigated the use of a novel MRI-pulse sequence described previously in Bour et al., (2017) to quantify both the displacement and temperature changes under various ultrasound sonication conditions and in different regions of the brain. The method was evaluated in vivo in a non-human primate under anesthesia using a single-element transducer (f = 850 kHz) in a setting that could mimic clinical applications. Acquisition was performed at 3 T on a clinical imaging system using a modified single-shot gradient echo EPI sequence integrating a bipolar motion-sensitive encoding gradient. Four slices were acquired sequentially perpendicularly or axially to the direction of the ultrasound beam with a 1-Hz update frequency and an isotropic spatial resolution of 2-mm. A total of twenty-four acquisitions were performed in three different sets of experiments. Measurement uncertainty of the sequence was investigated under different acoustic power deposition and in different regions of the brain. Acoustic simulation and thermal modeling were performed and compared to experimental data. ResultsThe sequence simultaneously provides relevant information about the focal spot location and visualization of heating of brain structures: 1) The sequence localized the acoustic focus both along as well as perpendicular to the ultrasound direction. Tissue displacements ranged from 1 to 2 μm. 2) Thermal rise was only observed at the vicinity of the skull. Temperature increase ranged between 1 and 2 °C and was observed delayed relative the sonication due to thermal diffusion. 3) The fast frame rate imaging was able to highlight magnetic susceptibility artifacts related to breathing, for the most caudal slices. We demonstrated that respiratory triggering successfully restored the sensitivity of the method (from 0.7 μm to 0.2 μm). 4) These results were corroborated by acoustic simulations. ConclusionsThe current rapid, multi-slice acquisition and real-time implementation of temperature and displacement visualization may be useful in clinical practices. It may help defining operational safety margins, improving therapy precision and efficacy. Simulations were in good agreement with experimental data and may thus be used prior treatment for procedure planning.

P14.28 First report on the combination of axitinib and Tumor Treating Fields (TTFields) in three patients with recurrent glioblastoma

Abstract BACKGROUND Adding Tumor Treating Fields (TTFields) to first-line therapy in glioblastoma (GBM) demonstrated significantly improved survival in the EF-14 trial. Furthermore, in a post-hoc analysis of the EF-14 trial, median overall survival increased significantly upon recurrence (rGBM) for patients treated with bevacizumab (Bev) and TTFields compared to Bev monotherapy. Axitinib (Axi) is an orally available tyrosine kinase inhibitor which is approved for the treatment of metastatic renal cell carcinoma. It has a high affinity and specificity for vascular endothelial growth factor receptors, thereby acting similar to Bev. In phase 2 trials, Axi improved response rate and progression free survival in rGBM patients compared to historical controls with a manageable toxicity profile. We report on three rGBM patients treated with TTFields and Axi (AxiTTFields). METHODS A 53-year-old male patient (#1) presented with a multifocal and consistently progressing GBM after initial surgery, radiochemotherapy (RCT) and after 4 cycles of temozolomide (TMZ), combined with TTFields. To meet the urgent need of an alternative treatment, Axi (5mg twice a day) was added to the treatment regimen. In a 46-year-old male patient (#2), an early progress occurred after surgery, RCT and 3 cycles of TMZ combined with TTFields. Similarly to #1, Axi was added to the treatment regimen. In a 61-year-old male patient (#3) with a rGBM after surgery and RCT at the time of the 6th cycle of TMZ, TTFields therapy was initiated at recurrence and treatment regimen was adapted to AxiTTFields. RESULTS In these three patients, AxiTTFields was safe and feasible. #1 and #2 were on AxiTTFields therapy for more than 8 months, presenting an improved neurological status with a partial response in the MRI 3 months initiating the combined treatment of AxiTTFields. #3 declined in his neurological status without any change in the MRI monitoring and died 2.4 months after initiating AxiTTFields. Although, Axi as well as TTFields may cause skin irritations, none were observed in this case series. With an average of 77 % in these three patients, the TTFields usage rate was above the independent prognostic threshold of 75 %, underlining the feasibility of this approach. There were no additional adverse events due to the combined therapy of AxiTTFields. CONCLUSION In summary, AxiTTFields was feasible and safe in three rGBM patients. As the addition of Axi to TTFields therapy is a promising approach, we plan to investigate the safety and feasibility of this combination in a pilot trial. Further studies might explore effects on outcome and survival of AxiTTFields in rGBM.

OS5.1 Phase I clinical trial with oncolytic virus DNX-2401 for DIPGs

Abstract BACKGROUND Despite our increased understanding of the genetic make-up and new therapies for pediatric high grade glioma (pHGG) and Diffuse Intrinsic Pontine Glioma (DIPG) the outcome remains grim. Delta-24-RGD (DNX-2401 in the clinic) has been tested for adult glioblastoma presenting a safe profile and promising efficacy. Recently our group has showed that the virus is safe and effective in preclinical models of pHGG and DIPG. Moreover, we showed that the virus is able to trigger an antitumor immune response. These outstanding preclinical results allowed us to propel a phase I clinical trial for newly diagnosed DIPGs (NCT03178032) where the patients received an intratumoral viral injection followed by standard radiotherapy. MATERIALS AND METHODS A phase I clinical trial with DNX-2401 for patients with newly diagnosed DIPG to assess the MTD is taking place in our hospital (N=12). Tumor biopsy is performed through the cerebellar peduncle, followed by virus injection. The virus is injected using a cannula, MEMS cannula (Alcyone Lifesciences) that prevents the reflux. Virus will be injected starting with 1010 pv. The trial is uncontrolled, unicentric with a 3 + 3 design. The objective of this trial is to determine the safety, tolerability, and toxicity of DNX-2401 in subjects with DIPG and to collect tumor samples of this type of tumor. Secondary endpoints are overall survival at 12 months (OS12), percentage of responses and induced immune response against tumor. The follow up includes close monitoring of neurological status, blood tests and brain MRI. If this trial shows evidence of safety and efficacy will propel a multicenter clinical trial. RESULTS All the clinical data from the trial available until September 2019 will be presented during the congress, to date 8 patients have been treated within the trial. Three patients were treated with the D1=1x1010vp and because the lack of toxicity we escalated to the D2= 5x1010vp. The procedure was well tolerated and safe. Patients were home 3–4 days after the injection. All the patients displayed a reduced tumor volume after combined treatment. We performed molecular studies in 6 out of the 8 patients. We are currently assessing the immune responses to the virus. CONCLUSIONS Information acquired within this clinical study would aid to understand the response of DIPGs to viral therapies and therefore to better tailor this strategy to improve the survival and the quality of life of pediatric brain tumors.

Initial Clinical Experience of Stereotactic Body Radiation Therapy (SBRT) For Liver Metastases, Primary Liver Malignancy, and Pancreatic Abdominal Nodal Recurrence with 4D-MRI based Online Adaptation and Real-Time MRI Monitoring using a 1.5 Tesla MR-Linac

The commercial introduction of a 1.5 MR equipped linear accelerator presents an opportunity to acquire MR images while simultaneously treating with external beam radiation therapy. We present the first in human experience treating patients for both liver and abdominal tumors using a 1.5 MR Linac. A commercially available 1.5 MR Linac was used to treat a total of 4 patients with abdominal tumors in our institution. Each patient consented to enroll in an advanced imaging protocol. A treatment checklist was followed during each fraction, with tasks time-stamped upon completion. Adaptive plans were based on pre-beam motion-averaged or mid-position images derived from respiratory-correlated 4D-MRI. Methodology applied included either adapt-to-position, or adapt-to-shape workflows. A parallel contouring strategy was employed using independent delineation software. Quantitative diffusion-weighted images, T2 mapping, and B0 maps were acquired during plan adaptation. Real-time motion monitoring was performed during beam-on. A comparison between the doses to normal organs at risk on the reference plan and the daily delivered plan was conducted. The median patient age was 70.5, two patients were male and two were female. Primary tumors treated (doses prescribed/fractions) included 1 liver melanoma metastatic lesion (45 Gy/3), 2 primary hepatocellular carcinomas (40-45 Gy/5), 1 upper abdominal nodal (pancreatic) recurrence (30 Gy/6). Two patients were treated with the adapt-to-position work flow, two patients were treated with the adapt-to-shape workflow. The median treatment time duration was approximately 50 minutes. For the liver lesions treated, the liver mean radiation dose was found to be lower on the adaptive plan as compared to the reference plan. In addition, for the abdominal nodal recurrence,accumulated dose to at risk GI structures was sufficiently below the reference plan dose, which permitted administration of an additional treatment fraction. We present a successful first in human experience of treating both an upper abdominal (pancreatic) nodal recurrence along with primary and secondary liver malignancies with a 1.5 MR Linear accelerator using adapt-to-position and adapt-to-shape strategies. Treatments were well tolerated by all patients. Fully quantitative MR imaging was acquired during the treatment course. Unique work flow elements and custom MR sequence utilization will be presented.

CEST MRI monitoring of tumor response to vascular disrupting therapy using high molecular weight dextrans

Magnetic Resonance in MedicineVolume 82, Issue 4 p. C1-C1 COVER IMAGEFree Access CEST MRI monitoring of tumor response to vascular disrupting therapy using high molecular weight dextrans First published: 12 July 2019 https://doi.org/10.1002/mrm.27901AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume82, Issue4October 2019Pages C1-C1 RelatedInformation

MRI of Patients with Cardiac Implantable Electronic Devices.

The purpose of this review is to clarify the risks associated with MRI exams for patients with cardiac implantable electronic devices (CIEDs) and to provide information regarding the MRI examination protocol for patients with CIEDs. Several prospective studies evaluated the feasibility of MRI exams for patients with CIEDs and reported no adverse events. These studies suggest that by following a specific MRI examination protocol and monitoring both CIED parameters and the patient's symptoms, an MRI exam can be performed by appropriately trained personnel with an acceptable benefit-to-risk ratio. Both MR unsafe and MR conditional CIEDs are commercially available, but there are no MR safe CIEDs. The potential risks faced by patients with CIEDs during an MRI exam are always present and warrant careful monitoring. Three magnetic fields in the MRI scanner interact with the device in ways that can damage the CIED or harm the patient. Due to safety concerns and out of an abundance of caution, the majority of MRI exams for patients with CIEDs are currently denied. However, when following a specific MRI exam protocol, these risks can be mitigated.

CEST MRI monitoring of tumor response to vascular disrupting therapy using high molecular weight dextrans.

Vascular disrupting therapy of cancer has become a promising approach not only to regress tumor growth directly but also to boost the delivery of chemotherapeutics in the tumor. An imaging approach to monitor the changes in tumor vascular permeability, therefore, has important applications for monitoring of vascular disrupting therapies. Mice bearing CT26 subcutaneous colon tumors were injected intravenously with 150 kD dextran (Dex150, diameter, d~ 20 nm, 375 mg/kg), tumor necrosis factor-alpha (TNF-α; 1 µg per mouse), or both (n = 3 in each group). The Z-spectra were acquired before and 2 h after the injection, and the chemical exchange saturation transfer (CEST) signals in the tumors as quantified by asymmetric magnetization transfer ratio (MTRasym ) at 1 ppm were compared. The results showed a significantly stronger CEST contrast enhancement at 1 ppm (∆MTRasym = 0.042 ± 0.002) in the TNF-α-treated tumors than those by Dex150 alone (∆MTRasym = 0.000 ± 0.005, P = 0.0229) or TNF-α alone (∆MTRasym = 0.002 ± 0.004, P = 0.0264), indicating that the TNF-α treatment strongly augmented the tumor uptake of 150 kD dextran. The MRI findings were verified by fluorescence imaging and immunofluorescence microscopy. High molecular weight dextrans can be used as safe and sensitive CEST MRI contrast agents for monitoring tumor response to vascular disrupting therapy and, potentially, for developing dextran-based theranostic drug delivery systems.

No increased cerebrovascular involvement in adult beta-thalassemia by advanced MRI analyses

Beta-thalassemia-related anemia and chronic hypercoagulative state are supposed to cause cumulative cerebrovascular damage with consequent parenchymal/vascular changes and functional impairment. However, recent conventional MRI/MR-angiography investigations failed to show an increased cerebrovascular involvement in beta-thalassemia patients managed according to current treatment guidelines, in spite of significantly decreased full-scale IQ scores. We therefore investigated those patients and controls by means of advanced quantitative MRI analyses (based on magnetization transfer and diffusion tensor imaging) searching for signs of possible cerebrovascular injuries undetected by conventional MRI/MR-angiography. The 3 T-MRI study protocol included diffusion tensor imaging and 3D-multi-echo FLASH sequences for magnetization transfer analysis.Whole-brain voxel-based analyses showed that magnetization transfer, fractional anisotropy, and mean, radial and axial diffusivity do not differ between healthy controls and beta-thalassemia patients (considered as a whole group or as distinct transfusion dependent and non-transfusion dependent subgroups). No correlation emerged between all the considered MRI metrics and cognitive findings (full-scale IQ) or the main clinical and laboratory data. According to our findings, adult neurologically-asymptomatic beta-thalassemia patients (regardless of clinical severity) do not seem to present an increased disease-related cerebrovascular vulnerability compared to healthy controls downsizing the need of regular brain MRI monitoring, at least when the current treatment guidelines are followed.

Profiling individual clinical responses by high-frequency serum neurofilament assessment in MS.

ObjectiveTo evaluate individual neurofilament light chain (NfL) variation over the time of disease course and the potential of NfL measurement to predict treatment response in patients with MS.MethodsWe investigated 15 patients with MS after immune reconstitution treatment with alemtuzumab (ATZ). Monthly serum NfL (sNFL) measurements were correlated with Expanded Disability Status Scale (EDSS), MRI, and relapse activity over an observational period of up to 102 months.ResultsBefore ATZ, sNfL was significantly increased in correlation with previous relapse/MRI activity. After ATZ, sNfL decreased quickly within the first 6 months. In patients classified as NEDA-3, sNfL declined and persisted at an individual low steady-state level of <8 pg/mL. During follow-up, 34 sNfL peaks with a >20 fold increase could be detected, which were associated with clinical or MRI disease activity. Even patient-reported relapse-suspicious symptoms, which have not been confirmed because relapses were accompanied by sNfL, increase, proposing sNfL assessment as a marker for relapse activity. sNfL started to increase earliest 5 months before, peaked at clinical onset, and recovered within 4–5 months. sNfL presented at higher levels in active patients requiring ATZ retreatment compared with responder patients. During 2 documented pregnancies, sNfL was at a low level, whereas a postpartum transient sNfL increase was seen without any signs of activity.ConclusionsThis study applied a long-term high-frequency sNfL assessment in an ATZ-treated cohort, allowing a holistic profiling on the individual level and highlighted that sNfL can eminently complement the individual clinical and MRI monitoring in clinical practice.

Сryodestruсtion of m8lign8nt liver lesions: MRI monitoring of trestment, preliminsry results

Aim : to аББевв dranges in liver pаrenсhymа in the еаг1у, tate аnd remote postoperative periods аfter сryodestruсtion (CD) of foсаl lesions by MRI with diffusion-weighted images (DWI). Mаteriаls аnd methods . Postoperative MRI monitoring wаs саrried out in 15 pаtients with mаlignаnt liver lesions. All pаtients were divided into two groups: with сomplete аnd inсumplete CD. All pаtients underwent MRI with dWi before surgery аnd in the postoperative period on the 1st dаy, 3 months, 6 аnd 12 months. Results. In group 1 - 100% “overlаp” of the pаthologiсаl foсus агеа of postoperative edemra ассording to T1WI аnd T2WI. Before surgery ~ ADC in the foсus wаs 0.86 mm 2 /s, in the 1st dаy - 1.00 mm 2 /s, 3 months - 1.03 mm 2 /s, 6 months - 1.30 mm 2 /s, 12 months - 1.30 mm 2 /s. Before surgery, the average size of the focus - 46 mm, in the 1st day - 57 mm, 3 months - 46 mm, 6 months - 45 mm, after 12 months - 39 mm. By the 12th month in group 1 ~ ADC in the focus increased by 51.20%, and the average size of the focus decreased by 16.00%. In group 2 - incomplete overlapping of the focus area of postoperative edema. Before surgery ~ ADC in the focus was 0.80 mm 2 /s, in the 1st day - 0.79 mm 2 / s, in 3 months -0.75 mm 2 /s, in 6 months - 0.66 mm 2 /s, in 12 months -0.55 mm 2 /s. Before surgery, the average size of the focus -44 mm, in the 1st day - 47 mm, in 3 months - 55 mm, in 6 months - 78 mm, after 12 months - 112 mm. 12 months after CD group 2 ~ ADC in the focus decreased by 31.30%, and the average size of the focus increased by 155.20% due to the continued growth of the tumor. Conclusion. MRI with DWI allows to assess changes in the liver and CD zone in the early, late and remote postoperative periods, to assess the completeness of the overlap zone of the CD focus and the dynamics of the continued growth of the tumor after incomplete CD.

Hybrid magneto-fluorescent nano-probe for live apoptotic cells monitoring at brain cerebral ischemia

α-Fe2O3 Magnetic nanoparticles (MNPs) have been synthesized, functionalized at silica that ends up with -NH2 group to form FMNPs. Conjugation of FMNPs with a fluorescently-labeled poly-caspase inhibitor valylalanylaspartic acid fluoromethyl ketone (SR-FLICA) which serves as a pan-caspase inhibitor was carried out to form finally a hybrid probe SR-FLICA-FMNPs. This probe could be used as a multimodal magneto-fluorescent platform for live apoptotic cells monitoring using MR and fluorescence imaging techniques. Characterization results of the as-synthesized MNPs and functionalized FMNPs by SEM, TEM, N2 isotherm, XRD and magnetic VSM showed that, a controlled morphological structure of MNPs could be synthesized with cubic-shaped, ferromagnetic, base-centered orthorhombic space group R3c and average size of 45.8 ± 3.2 and 50.3 ± 1.6 nm for MNPs and FMNPs, respectively. Phantom MRI experimental results of the examined MNPs and FMNPs confirmed the concentration dependency nature of T2 signal reduction. In addition, in vitro and in vivo sensing studies on our conjugated hybrid multifunctional probe SR-FLICA-FMNPs using 9 L gliosarcoma cells confirmed that; it could positively intact within the astrocytes and the nuclei of the apoptotic cells taking into account the starting material's cytotoxicity. Several histo-chemical protocols could be examined to confirm such behavior. Confocal and fluorescence microscopes' results of the histological stained apoptotic cells confirmed positive and specific expressions of our designed probe. MRI monitoring results of apoptotic rat models after focal brain transient cerebral ischemia showed a remarkable time-dependent reduction of T2* weighted signal up to 4 h indicating that our newly designed hybrid probe has long blood circulation and could be used as a future contrasting agent. Moreover, the distribution of our probe was evaluated by subtracting the T2* signal images before and after injection with SR-FLICA-FMNPs and was significantly correlated with the histological findings by staining via terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end labeling. Moreover, clearance study confirmed that; our magneto-fluorescent hybrid probe could be cleared through liver Kupffer cells. Thus; the newly developed SR-FLICA-FMNPs could be considered as a future multifunctional probe for in vitro and in vivo apoptotic cells monitoring.

Bacteria-Responsive Nanoliposomes as Smart Sonotheranostics for Multidrug Resistant Bacterial Infections.

Rapid emergence of multidrug resistant (MDR) "superbugs" poses a severe threat to global health. Notably, undeveloped diagnosis and concomitant treatment failure remain highly challenging. Herein, we report a sonotheranostic strategy to achieve bacteria-specific labeling and visualized sonodynamic therapy (SDT). Using maltohexaose-decorated cholesterol and bacteria-responsive lipid compositions, a smart nanoliposomes platform (MLP18) was developed for precise delivery of purpurin 18, a potent sonosensitizer proved in this study. Taking advantage of the bacteria-specific maltodextrin transport pathway, the prepared MLP18 can specifically target the bacterial infection site and accurately distinguish the foci from sterile inflammation or cancer with a highly selective fluorescence/photoacoustic signal on the bacteria-infected site of mice. Moreover, the bacteria-responsive feature of MLP18 activated an efficient release and internalization of high concentration sonosensitizer into bacterial cells, resulting in effective sonodynamic elimination of MDR bacteria. In situ MRI monitoring visualized such potent sonodynamic activity and indicated that MLP18-mediated SDT could successfully eradicate inflammation and abscess from mice with bacterial myositis. In view of the above advantages, the developed nanoliposomes may serve as a promising sonotheranostic platform against MDR bacteria in the areas of healthcare.

Microwave ablation of hepatic malignant tumors using 1.5T MRI guidance and monitoring: feasibility and preliminary clinical experience

Purpose: To evaluate the feasibility and therapeutic efficacy of 1.5-T MRI-guided and monitored microwave ablation in patients with hepatic malignant tumors.Materials and Methods: This retrospective study was approved by the ethics committee of the First Affiliated Hospital of Fujian Medical University. Thirty-five patients (32 men, three women) with 48 lesions (maximum diameter < 3 cm) underwent microwave ablation under the guidance and monitoring of a 1.5-T MRI. The MRI-compatible microwave generator was appended with a magnetic shield case, and the cable was combined with a choke coil for shielding the Larmor processing frequency. The average age of the patients was 56.51 ± 11.36 years (31–77 years). Twenty-eight patients (37 lesions) displayed hepatocellular carcinoma and seven patients (11 lesions) had metastatic liver carcinoma. The mean maximum tumor diameter was 12.31 ± 4.72 mm (range 5.0–25.7 mm).Results: MRI scans were performed simultaneously without electromagnetic interference during ablation. The average maximum diameter of the hypointense zone of the last monitored T2WI sequence, hypointense zone of post-procedure T2WI sequence, and hyperintense zone of post-procedure T1WI were 28.82 ± 7.58 mm, 29.79 ± 7.91 mm, and 28.28 ± 8.37 mm, respectively, with no observed statistical difference (F = 0.434, p = .649). The technical success rate was 100%. The average follow-up duration was 11.43 ± 5.29 (4–33) months. The technique efficacy rate was 100%.Conclusion: MRI-guided and monitored microwave ablation of hepatic malignant tumors is feasible and potentially safe and effective.Key pointsMRI-guided microwave ablation of hepatic malignant tumors is feasible.The MRI monitoring scan could accurately reflect the scope of ablation lesion.On T1WI, the ablation lesions of liver showed the ‘target sign’.

A light-responsive liposomal agent for MRI contrast enhancement and monitoring of cargo delivery.

Medical magnetic resonance imaging (MRI) produces high-resolution anatomical images of the human body, but has limited capacity to provide useful molecular information. The light-responsive, liposomal MRI contrast agent described herein could be used to provide an intrinsic theranostic aspect to MRI and enable tracking the distribution and cargo release of drug delivery systems upon light-triggered activation.