Electroporation is a well-known phenomenon that occurs at the cell membrane when cells are exposed to high-intensity electric pulses. Depending on electric pulse amplitude and number of pulses, ...applied electroporation can be reversible with membrane permeability recovery or irreversible. Reversible electroporation is used to introduce drugs or genetic material into the cell without affecting cell viability. Electrochemotherapy refers to a combined treatment: electroporation and drug injection to enhance its cytotoxic effect up to 1000-fold for bleomycin. Since several years, electrochemotherapy is gaining popularity as minimally invasive oncologic treatment. The adoption of electrochemotherapy procedure in interventional oncology poses several unsolved questions, since suitable tumor histology and size as well as therapeutic efficacy still needs to be deepen. Electrochemotherapy is usually applied in palliative settings for the treatment of patients with unresectable tumors to relieve pain and ameliorate quality of life. In most cases, it is used in the treatment of advanced stages of neoplasia when radical surgical treatment is not possible (eg, due to lesion location, size, and/or number). Further, electrochemotherapy allows treating tumor nodules in the proximity of important structures like vessels and nerves as the treatment does not involve tissue heating. Overall, the safety profile of electrochemotherapy is favorable. Most of the observed adverse events are local and transient, moderate local pain, erythema, edema, and muscle contractions during electroporation. The aim of this article is to review the recent published clinical experiences of electrochemotherapy use in deep-seated tumors with particular focus on liver cases. The principle of electrochemotherapy as well as the application to cutaneous metastases is briefly described. A short insight in the treatment of bone metastases, unresectable pancreas cancer, and soft tissue sarcoma will be given. Preclinical and clinical studies on treatment efficacy with electrochemotherapy of hepatic lesions and safety of the procedure adopted are discussed.
The application of navigational systems has the potential to improve percutaneous interventions. The accuracy of ablation probe placement can be increased and radiation doses reduced. Two different ...types of systems can be distinguished, tracking systems and robotic systems. This review gives an overview of navigation devices for clinical application and summarizes first findings in the implementation of navigation in percutaneous interventions using irreversible electroporation. Because of the high number of navigation systems, this review focuses on commercially available ones.
Abstract
Gadoxetic acid (Gd-EOB-DTPA) is a paramagnetic MRI contrast agent with raising popularity and has been used for evaluation of imaging-based liver function in recent years. In order to verify ...whether liver function as determined by real-time breath analysis using the intravenous administration of
13
C-methacetin can be estimated quantitatively from Gd-EOB-DTPA-enhanced MRI using signal intensity (SI) values. 110 patients underwent Gd-EOB-DTPA-enhanced 3-T MRI and, for the evaluation of liver function, a
13
C-methacetin breath test (
13
C-MBT). SI values from before (SI
pre
) and 20 min after (SI
post
) contrast media injection were acquired by T1-weighted volume-interpolated breath-hold examination (VIBE) sequences with fat suppression. The relative enhancement (RE) between the plain and contrast-enhanced SI values was calculated and evaluated in a correlation analysis of
13
C-MBT values to SI
post
and RE to obtain a SI-based estimation of
13
C-MBT values. The simple regression model showed a log-linear correlation of
13
C-MBT values with SI
post
and RE (p < 0.001). Stratified by 3 different categories of
13
C-MBT readouts, there was a constant significant decrease in both SI
post
(p ≤ 0.002) and RE (p ≤ 0.033) with increasing liver disease progression as assessed by the
13
C-MBT. Liver function as determined using real-time
13
C-methacetin breath analysis can be estimated quantitatively from Gd-EOB-DTPA-enhanced MRI using SI-based indices.
Gadoxetic acid-enhanced magnetic resonance imaging has become a useful tool for quantitative evaluation of liver capacity. We report on the importance of intrahepatic fat on gadoxetic acid-supported ...T1 mapping for estimation of liver maximum capacity, assessed by the realtime
C-methacetin breathing test (
C-MBT). For T1 relaxometry, we used a respective T1-weighted sequence with two-point Dixon water-fat separation and various flip angles. Both T1 maps of the in-phase component without fat separation (T1_in) and T1 maps merely based on the water component (T1_W) were generated, and respective reduction rates of the T1 relaxation time (rrT1) were evaluated. A steady considerable decline in rrT1 with progressive reduction of liver function could be observed for both T1_in and T1_W (p < 0.001). When patients were subdivided into 3 different categories of
C-MBT readouts, the groups could be significantly differentiated by their rrT1_in and rrT1_W values (p < 0.005). In a simple correlation model of
C-MBT values with T1_inpost (r = 0.556; p < 0.001), T1_Wpost (r = 0.557; p < 0.001), rrT1_in (r = 0.711; p < 0.001) and rrT1_W (r = 0.751; p < 0.001), a log-linear correlation has been shown. Liver maximum capacity measured with
C-MBT can be determined more precisely from gadoxetic acid-supported T1 mapping when intrahepatic fat is taken into account. Here, T1_W maps are shown to be significantly superior to T1_in maps without separation of fat.
The diagnostic value of Doppler ultrasonography of the portal vein for the evaluation of liver function is still contradictory.
Aim of this study was to test the relationship between clinical liver ...function tests based on MRI and breath testing and blood flow in the portal vein.
The portal vein velocity was measured by color coded Doppler ultrasonography (CCDS) and tested against the relative enhancement (RE), a MRI-based index of liver function. The signal intensity in the liver parenchyma was assessed before (pre) and after (post) administration of contrast agent, the RE was calculated afterwards. Further, the liver function was also assessed using a 13C-Methacetin-based breath test. The blood flow in the portal vein was tested for possible correlation applying Pearson's correlation coefficient.
Using CCDS, all patients show a hepatopetal portal blood flow. The portal vein velocity is decreasing with progression of liver damage and there was a significant correlation of portal velocity with SI post (r = 0.411, p = 0.024). However, the portal velocity did not correlate significantly with the 13C-MBT readout (r = 0.233; p = 0.216), SI pre (r = 0.271, p = 0.147) or the relative enhancement (r = 0.303; p = 0.103).
The results of this proof-of-principle study indicate that CCDS-based assessment of portal velocity is of only limited value for the evaluation of liver function.
Contrast enhanced magnetic resonance imaging (MRI) is able to assess liver function by characteristic changes of signal intensity (SI).The aim was to evaluate dynamic contrast-enhanced SI-indices of ...the abdominal aorta, portal vein and liver.
72 patients underwent Gd-EOB-DTPA-enhanced MRI and a 13C-methacetin-based liver breath test (13C-MBT) for evaluation of liver function. Region-of-interest measurements in the liver, abdominal aorta and portal vein during native, arterial (AP), late arterial (LAP), portal venous (PVP) and hepatobiliary phase (HBP) were applied to analyze SI-indices in T1-weighted volume-interpolated breath-hold examination (VIBE) sequences with fat-suppression and relative enhancement (RE) analysis was performed.
The liver (p < 0.001), the portal vein (p < 0.001) and abdominal aorta (p = 0.002) showed significant decrease of REs with decreasing liver function. An increasing trend between logarithmic values of 13C-MBT and REs of hepatic parenchyma (HBP; r = 0.662, p < 0.001), portal vein (PVP; r = 0.532, p < 0.001) and abdominal aorta (PVP; r = 0.421, p < 0.001) was observed.
RE measurements of the hepatic parenchyma proofed to be a trustable evaluation method for liver function evaluation. In accordance with liver function, changes of REs in the portal vein and abdominal aorta occur.
Gadoxetic acid (Gd-EOB-DTPA) is a paramagnetic MRI contrast agent with raising popularity and has been used for evaluation of imaging-based liver function in recent years. In order to verify whether ...liver function as determined by real-time breath analysis using the intravenous administration of
C-methacetin can be estimated quantitatively from Gd-EOB-DTPA-enhanced MRI using signal intensity (SI) values. 110 patients underwent Gd-EOB-DTPA-enhanced 3-T MRI and, for the evaluation of liver function, a
C-methacetin breath test (
C-MBT). SI values from before (SI
) and 20 min after (SI
) contrast media injection were acquired by T1-weighted volume-interpolated breath-hold examination (VIBE) sequences with fat suppression. The relative enhancement (RE) between the plain and contrast-enhanced SI values was calculated and evaluated in a correlation analysis of
C-MBT values to SI
and RE to obtain a SI-based estimation of
C-MBT values. The simple regression model showed a log-linear correlation of
C-MBT values with SI
and RE (p < 0.001). Stratified by 3 different categories of
C-MBT readouts, there was a constant significant decrease in both SI
(p ≤ 0.002) and RE (p ≤ 0.033) with increasing liver disease progression as assessed by the
C-MBT. Liver function as determined using real-time
C-methacetin breath analysis can be estimated quantitatively from Gd-EOB-DTPA-enhanced MRI using SI-based indices.
Objective
Anti–N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis with a characteristic neuropsychiatric syndrome and severe and prolonged clinical courses. In contrast, ...standard clinical magnetic resonance imaging (MRI) remains normal in the majority of patients. Here, we investigated structural and functional brain changes in a cohort of patients with anti‐NMDAR encephalitis.
Methods
Twenty‐four patients with established diagnosis of anti‐NMDAR encephalitis and age‐ and gender‐matched controls underwent neuropsychological testing and multimodal MRI, including T1w/T2w structural imaging, analysis of resting state functional connectivity, analysis of white matter using diffusion tensor imaging, and analysis of gray matter using voxel‐based morphometry.
Results
Patients showed significantly reduced functional connectivity of the left and right hippocampus with the anterior default mode network. Connectivity of both hippocampi predicted memory performance in patients. Diffusion tensor imaging revealed extensive white matter changes, which were most prominent in the cingulum and which correlated with disease severity. In contrast, no differences in T1w/T2w structural imaging and gray matter morphology were observed between patients and controls.
Interpretation
Anti‐NMDAR encephalitis is associated with characteristic alterations of functional connectivity and widespread changes of white matter integrity despite normal findings in routine clinical MRI. These results may help to explain the clinicoradiological paradox in anti‐NMDAR encephalitis and advance the pathophysiological understanding of the disease. Correlation of imaging abnormalities with disease symptoms and severity suggests that these changes play an important role in the symptomatology of anti‐NMDAR encephalitis. Ann Neurol 2013;74:257–265
A total synthesis of the cyclic lipodepsipeptide natural product orfamide A was achieved. By developing a synthesis format using an aminoacid ester building block and SPPS protocol adaptation, a ...focused library of target compounds was obtained, in high yield and purity. Spectral and LC‐HRMS data of all library members with the isolated natural product identified the 5Leu residue to be d‐ and the 3’‐OH group to be R‐configured. The structural correction of orfamide A by chemical synthesis and analysis was confirmed by biological activity comparison in Chlamydomonas reinhardtii, which indicated compound configuration to be important for bioactivity. Acute toxicity was also found against Trypanosoma brucei, the parasite causing African sleeping sickness.
For the total synthesis of orfamide A an efficient synthesis format for cyclic lipodepsipeptide natural products on solid phase was developed. A strategy using side chain anchoring, an ester building block, and O→N acyl migration suppression enabled high‐yielding synthesis on solid support and facilitated compound library synthesis. The configuration of the proposed structure of orfamide A was corrected at two positions. Studies in Chlamydomonas algae uncovered the impact of orfamide A stereochemistry on compound bioactivity.
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