Prostate cancer treatment with Irreversible Electroporation (IRE): Safety, efficacy and clinical experience in 471 treatments.

BACKGROUND: Irreversible Electroporation (IRE) is a novel image-guided tissue ablation technology that induces cell death via very short but strong pulsed electric fields. IRE has been shown to have preserving properties towards vessels and nerves and the extracellular matrix. This makes IRE an ideal candidate to treat prostate cancer (PCa) where other treatment modalities frequently unselectively destroy surrounding structures inducing severe side effects like incontinence or impotence. We report the retrospective assessment of 471 IRE treatments in 429 patients of all grades and stages of PCa with 6-year maximum follow-up time. MATERIAL AND FINDINGS: The patient cohort consisted of low (25), intermediate (88) and high-risk cancers (312). All had multi-parametric magnetic resonance imaging, and 199 men had additional 3D-mapping biopsy for diagnostic work-up prior to IRE. Patients were treated either focally (123), sub-whole-gland (154), whole-gland (134) or for recurrent disease (63) after previous radical prostatectomy, radiation therapy, etc. Adverse effects were mild (19.7%), moderate (3.7%) and severe (1.4%), never life-threatening. Urinary continence was preserved in all cases. IRE-induced erectile dysfunction persisted in 3% of the evaluated cases 12 months post treatment. Mean transient IIEF-5-Score reduction was 33% within 12-month post IRE follow-up and 15% after 12 months. Recurrences within the follow-up period occurred in 10% of the treated men, 23 in or adjacent to the treatment field and 18 outside the treatment field (residuals). Including residuals for worst case analysis, Kaplan Maier estimation on recurrence rate at 5 years resulted in 5.6% (CI95: 1.8-16.93) for Gleason 6, 14.6% (CI95: 8.8-23.7) for Gleason 7 and 39.5% (CI95: 23.5-61.4) for Gleason 8-10. CONCLUSION: The results indicate comparable efficacy of IRE to standard radical prostatectomy in terms of 5-year recurrence rates and better preservation of urogenital function, proving the safety and suitability of IRE for PCa treatment. The data also shows that IRE, besides focal therapy of early PCa, can also be used for whole-gland ablations, in patients with recurrent PCa, and as a problem-solver for local tumor control in T4-cancers not amenable to surgery and radiation therapy anymore.

Oxygen-induced MR signal changes in murine tumors.

Breathing of 100% oxygen was used to challenge vascular autoregulation in 14 mice with either osteosarcomas (n = 6) or mammary carcinomas (n = 8). Reproducible and statistically significant signal intensity changes of -29 +/- 6% to +35 +/- 3% were observed on heavily T2*-weighted images in the tumors during the oxygen challenge. No significant changes were observed in muscle. For the mammary carcinomas a higher percentage of tumor voxels showed significant signal-intensity decrease (31 +/- 8%) compared to the percentage of voxels showing a signal-intensity increase (22 +/- 3%). In contrast, for the osteosarcomas, a higher percentage of tumor voxels showed signal-intensity increase (52 +/- 9%) compared to the percentage of voxels showing signal-intensity decrease (27 +/- 9%). The regional distribution of these signal intensity changes did not correlate with the signal pattern on T1-, T2-,and T2*-weighted and Gd-DTPA enhanced images acquired without breathing 100% oxygen. Most likely, the signal intensity changes represented the inability of the tumor's neovascularization for autoregulation during the oxygen challenge, particularly in hypoxic regions. Although further investigation is needed, the findings that malignant tumor tissue showed signal intensity changes, whereas normal muscle tissue did not, suggests that this technique may prove useful in distinguishing benign from malignant tissue.

Non-invasive temperature mapping using MRI: comparison of two methods based on chemical shift and T1-relaxation.

PURPOSE: To implement and evaluate the accuracy of non-invasive temperature mapping using MRI methods based on the chemical shift (CS) and T1 relaxation in media of various heterogeneity during focal (laser) and external thermal energy deposition. MATERIALS AND METHODS: All measurements were performed on a 1.5 T superconducting clinical scanner using the temperature dependence of the water proton chemical shift and the T1 relaxation time. Homogeneous gel and heterogeneous muscle phantoms were heated focally with a fiberoptic laser probe and externally of varying degree ex vivo by water circulating in a temperature range of 20-50 degrees C. Magnetic resonance imaging data were compared to simultaneously recorded fiberoptic temperature readings. RESULTS: Both methods provided accurate results in homogeneous media (turkey) with better accuracy for the chemical shift method (CS:+/-1.5 degrees C, T1:+/-2.0 degrees C). In gel, the accuracy with the CS method was +/-0.6 degrees C. The accuracy decreased in heterogeneous media containing fat (T1:+/-3.5 degrees C, CS: +5 degrees C). In focal heating of turkey muscle, the accuracy was within 1.5 degrees C with the T1 method. CONCLUSION: Temperature monitoring with the chemical shift provides better results in homogeneous media containing no fat. In fat tissue, the temperature calculation proved to be difficult.

Gadolinium-enhanced magnetic resonance angiography of the pelvis in patients with erectile impotence.

This study evaluated the potential of contrast-enhanced digital-subtraction magnetic resonance angiography (CE-DS-MRA) for noninvasive angiographic delineation of the arterial supply of the penis in patients with erectile dysfunction. After induction of an erection with prostaglandin E, a three-dimensional fast imaging with steady-state precision (FISP) sequence with TE of 1.8-2 milliseconds, TR of 4.4-5 milliseconds, and flip angle of 40 degrees-60 degrees was used to obtain high-resolution angiograms of the pelvis and penis during the injection of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) 0.3 mmol/kg body weight, within 30-50 seconds. DS maximum intensity projections (MIPs) and multiplanar reconstructions (MPRs) were compared with clinical work-up and directional Doppler ultrasound in 11 patients. In all 11 patients (100%), the arterial supply of the penis could be delineated from the aortic bifurcation via the iliac and internal pudendal arteries to the dorsal and deep penile arteries. Of the 22 internal pudendal arteries, 6 (27%) were occluded on CE-DS-MRA and 5 (23%) had stenoses, of which 4 (18%) were greater than 50%. In 7 patients (64%) good correlation between CE-DS-MRA and clinical findings and/or Doppler ultrasound was found; in 2 patients (18%), the correlation was moderate, and in 2 patients (18%) results were discrepant. In 6 patients (55%), MRA provided additional information to the clinical and Doppler ultrasound work-up. CE-DS-MRA can delineate small vessels such as the internal pudendal and penile arteries and thus has the potential to become a noninvasive angiography method in the work-up of erectile impotence.

Pathologic conditions in the small bowel: findings at fat-suppressed gadolinium-enhanced MR imaging with an optimized suspension of oral magnetic particles.

Depiction of small-bowel pathologic conditions was optimized with use of a negative luminal contrast agent, spectral fat suppression, and gadolinium enhancement in an excised gut phantom. The method was applied in nine patients in conjunction with standard enteroclysis examinations. Bulk susceptibility effects of oral magnetic particles were canceled with use of a diamagnetic methylcellulose suspension. In the ileum, fat suppression and contrast between bowel wall and lumen was judged good or excellent in eight and nine patients, respectively. In eight of nine patients, additional mesenteric findings were depicted.

[Contrast medium enhanced magnetic resonance angiography. Theory, technique and practical implementation]. / Kontrastmittelverstärkte Magnetresonanzangiographie. Theorie, Technik und praktische Durchführung.

Contrast enhanced (CE) magnetic resonance angiography affords angiographic depiction of extended vascular territories with high quality and diagnostic value. A prerequisite is the fast acquisition of a three-dimensional gradient-echo data set during the injection of a bolus of a T1-shortening contrast agent. We describe the dependence of the quality of CE-MRA on technical parameters of different MR-scanners and consider some fundamental facts and practical guidelines concerning the contrast agent injection.

[Gadolinium-enhanced magnetic resonance angiography of abdominal blood vessels]. / Gadolinium-verstärkte Magnetresonanzangiographie der Abdominalgefässe.

Contrast enhanced (CE) magnetic resonance angiography (MRA) provides high resolution angiograms within 20-40 sec. The technique is based on the acquisition of heavily T1-weighted three-dimensional (3D) gradient-echo data sets (FISP) with ultrashort echo-(< 2ms) and repetition times (< 5 ms) during arterial phase of an intravenously injected bolus of a T1-shortening agent such as Gd-DTPA. For MR-angiography of abdominal vessels CE-MRA is better suited than "time-of flight" (TOF) and phase-contrast (PC) MRA because motional artifacts can be obviated with breath-held acquisitions. We have optimised the technique and evaluated its potential for angiography of the abdominal aorta and its branches as well as the portal vein and its tributaries. Whilst CE-MRA provides reliable diagnostic accuracy in the aorta and the proximal sections of its branches, small peripheral arteries cannot be assessed accurately. The portal vein and its tributaries can often be depicted better with CE-MRA than with conventional angiography but, like conventional angiography, CE-MRA is hampered by slow and reversed flow, conditions under which TOF or "true FISP" MRA may perform bst. We have also investigated FLASH-echo-planar imaging (EPI) hybrid techniques, a further technical development which due to shorter acquisition times of 12-15 sec. allows semi-dynamic imaging of the arterial and venous phase and provide better vessel contrast due to the use of fat-suppression.

[Qualitative and quantitative determination of regional myocardial perfusion with magnetic resonance tomography]. / Qualitative und quantitative Bestimmung der regionalen Myokardperfusion mittels Magnetresonanztomographie.

PURPOSE: Purpose of this study was to test a triple slice saturation recovery turbo FLASH sequence for myocardial perfusion imaging. In addition data-evaluation-tools for qualitative and quantitative perfusion parameters are presented and preliminary tested. MATERIAL AND METHODS: We examined 8 healthy volunteers and 4 patients with myocardial infarction. Parameters of the saturation recovery turbo FLASH sequence were as follows: TR = 2.5 msec, TE = 1.2 msec, alpha = 8 degrees, 3 slices, thickness 10 mm. For data analysis signal-intensity time curves were calculated pixel by pixel and evaluated for signal-intensity-increase over baseline and signal-intensity-upslope. Images were displayed color-coded. For quantitative data analysis we used the indicator dilution theory and developed a deconvolution algorithm which takes the arterial input function into account to calculate the myocardial mean transit time (MTT). RESULTS: The color-coded parametermaps showed uniform conditions in normal myocardium of volunteers, but reduced signal-intensity-increase over baseline and signal-intensity-upslope for infarcted areas in patients. The MTTs calculated using our algorithm were significantly shorter than those assessed with previous methods and matched better with values derived from literature. Infarcted areas show prolonged MTTs in comparison to normal myocardium. CONCLUSION: A triple slice saturation recovery turbo FLASH sequence is suitable for myocardial perfusion imaging. Color-coded parametermaps can visualize hypoperfused areas. For calculating myocardial MTTs using indicator dilution therapy a deconvolution algorithm is necessary.

[CT subtraction angiography (CTSA). Results with an automated "elastic" subtraction algorithm]. / CT-Subtraktionsangiographie (CTSA). Ergebnisse mit einem automatisierten "elastischen" Subtraktionsalgorithmus.

PURPOSE: To develop and implement a method to obtain digital subtraction (DS) spiral computed tomography angiograms (SCTA) in order to avoid superimposition of bony structures and vascular calcifications on SCTA maximum intensity projections (MIPs) and shaded surface display (SSD). METHOD: Two SCTA data sets, one before and one during the injection of a contrast agent bolus, were obtained with identical scan parameters. Since ordinary subtraction of the two data sets fails to reliably separate bones and calcifications from the vascular lumen because of motion, a so-called elastic subtraction procedure was designed to correct 3D misregistration between the two data sets. It automatically accommodates for local position changes between baseline and contrast images, including regionally inconsistent non-linear displacements and arbitrary rotations. This method was tested in seven patients and evaluated against ordinary DS in terms of image quality and artifacts. RESULTS: In all patients "elastic" CTSA proved superior to ordinary DS. It provides automated and reliable separation of vessels from bones and calcifications. This improves the delineation of vessels in the neck and the skull base and of intracranial vessels. DS-SCTA facilitates MIPs and SSD without artifacts introduced by thresholding. CONCLUSION: Elastic DS-SCTA is a robust method for automated unmasking of vessels from bones and warrants clinical trials and comparison with MR- and conventional angiography.

Choledocholithiasis after Billroth II surgery: MR cholangiographic diagnosis.

In this case of choledocholithiasis in a patient with previous Billroth-II surgery and cholecystectomy we demonstrate the advantages of a heavily T2-weighted half-Fourier turbo-spin-echo (HASTE) sequence. This technique allows thin-slice snapshot imaging with 1.4 s per slice eliminating motion artifacts and still has the necessary heavy T2-weighting to depict biliary fluid with high contrast. In the presented case endoscopic retrograde cholangiography (ERCP) could not be performed prior to MRI due to technical problems. In a second attempt, ERCP was successful and a common bile duct stone as diagnosed by MRI before could be removed. We conclude that HASTE snapshot MR cholangiography can be used as a clinically valuable tool when other noninvasive methods are not diagnostic.

Magnetic resonance imaging of the female pelvis. New circularly polarized body array coil versus standard body coil.

RATIONALE AND OBJECTIVES: The authors compare the value of a new circularly polarized body array coil (BAC) system with a standard body coil (BC) for high-resolution magnetic resonance imaging of the female pelvis. METHODS: Twenty patients with cervical cancer were examined with a BC and BAC. Imaging parameters were kept constant (sagittal T2-weighted turbo spin-echo: repetition time = 4000 mseconds; effective echo time = 99 mseconds; 160 x 160 mm field of view; 256 x 256 matrix; 0.63 x 0.63 mm pixel size; 4-mm slice thickness). Images were scored for lesion-to-organ delineation and overall image quality/ artifacts using a scale from 5 to 1 (excellent to poor). Signal-to-noise (S/N) ratios for different tissues (tumor, uterus, vagina, rectum, muscle, and fat) as well as contrast-to-noise (C/N) ratios between tumor and (1) uterus, (2) vagina, and (3) rectum were calculated. Magnetic resonance tumor staging was performed according to the International Federation of Gynecology and Obstetrics (FIGO) classification. RESULTS: Using the BAC, S/N and C/N ratios increased significantly compared with the BC (S/N: 2.7-3.4-fold increase for all organs evaluated, P < 0.001: C/N: tumor versus uterus 2.4-fold, P < 0.01; tumor versus vagina 6.1-fold, P < 0.001; tumor versus rectum 3.1-fold, P < 0.01). This resulted in an improved overall image quality (average ratings: BAC-4.3 points; BC-2.6 points; P < 0.001). Lesion-to-organ delineation (average ratings: BAC 4.3-4.1 points, BC 3.5-2.7 points for all organs evaluated; P < 0.001) was increased noticeably on BAC images. No significant difference was found for staging accuracy. CONCLUSIONS: Circularly polarized BAC provide superior S/N and C/N ratios and improve lesion conspicuity compared with standard BC.

[MRI monitoring before, during and after interstitial laser-induced hyperthermia of benign prostatic hyperplasia. Initial clinical experiences]. / MRT-Monitoring vor, während und nach der interstitiellen laserinduzierten Thermotherapie der benignen Prostatahyperplasie. Erste kliniscne Erfahrungen.

PURPOSE: To assess the clinical value of MRI in patients with benign prostatic hyperplasia (BPH) before, during, and after interstitial laser-induced thermotherapy (LITT) of the prostate. METHODS: Ten patients with symptomatic BPH had MRI examinations of the prostate 48 h before and after LITT. Online monitoring with MRI at 1.5 T of interstitial Nd:YAG laser energy deposition in the prostate was performed in two patients, repeating a T1-weighted FLASH sequence (TR 100 ms, TE 5 ms, flip angle 90 degrees) every 20 s. Follow-up MRI examinations 2-3 weeks, 6-8 weeks, and 6-12 months after LITT were carried out in eight patients, using T2-weighted FSE images and contrast-enhanced T1-weighted SE images. RESULTS: The prostate was well delineated in all patients on T2-weighted FSE images, with a rather homogeneous peripheral gland and an inhomogeneous central gland. Volume measurements yielded reproducibilities of 3.2%-4.7%. Signal intensity in the FLASH sequence decreased during LITT, both in the prostate in vivo and in specimens of bovine prostate and seminal vesicles in vitro, with signal developments running in parallel. Areas of energy deposition and signal alteration were not sharply delineated. The latter margin of the laser-induced lesions could not be predicted from the FLASH images, while the tip of the laser fibre was easily recognized. Contrast-enhanced T1-weighted MR images immediately after LITT clearly demarcated low signal intensity laser lesions from high signal intensity surrounding prostate tissue. Follow-up examinations showed a decrease of 20% of prostate volume over a period of 6-12 months after LITT. Correlation between prostate volume development and lesion volume alteration was 0.85-0.90 (P = 0.002-0.007) at all follow-up times. CONCLUSIONS: MRI allows rather precise recognition of intraprostatic alterations after LITT, including volume changes over a period of up to 1 year after therapy that can be predicted immediately after LITT. While laser energy deposition in the prostate can be monitored by MRI with T1-weighted FLASH sequences as a function of temperature alteration, it is not possible to determine the lesion margins immediately from the FLASH images. Online temperature development map generation will be necessary to influence on-going LITT procedures with MRI.

Single-shot T1- and T2-weighted magnetic resonance imaging of the heart with black blood: preliminary experience.

PURPOSE: To implement and evaluate two robust methods for T1- and T2-weighted snapshot imaging of the heart with data acquisition within a single heart beat and suppression of blood signal. METHODS: Both T1- and T2-weighted diastolic images of the heart can be obtained with half Fourier single-shot turbo spin echo (HASTE) and turbo fast low-angle shot (turboFLASH) sequences, respectively, in less than 350 ms. Signal from flowing blood in the ventricles and large vessels can be suppressed by a preceding inversion recovery preparing pulse pair (PRESTO). Fifteen volunteers and five patients have been evaluated quantitatively for signal-to-noise ratio (SNR) contrast-to-noise ratio (CNR) and flow void and qualitatively for image quality, artifacts, and black-blood effect. RESULTS: Both PRESTO-HASTE and PRESTO-turboFLASH achieved consistently good image quality and blood signal suppression. In contrast to gradient-echo (GRE) echo-planar imaging techniques, (EPI) HASTE and turboFLASH are much less sensitive to local susceptibility differences in the thorax, resulting in a more robust imaging technique without the need for time-consuming system tuning. Compared to standard spin-echo sequences with cardiac triggering. HASTE and turboFLASH have significantly shorter image acquisition times and are not vulnerable to respiratory motion artifacts. CONCLUSION: PRESTO-HASTE and PRESTO-turboFLASH constitute suitable methods for fast and high-quality cardiac magnetic resonance imaging (MRI).

[Gadolinium-enhanced magnetic resonance angiography with ultra-short echo times. Initial experiences]. / Gadoliniumverstärkte Magnetresonanzangiographie mit ultrakurzen Echozeiten. Erste Erfahrungen.

Magnetic resonance angiography (MRA) using three-dimensional (3D) gradient-echo sequences with ultra-short echotimes (USTE; 2 ms) and luminal enhancement of vessels with a gadolinium bolus affords the depiction of extended vascular territories with high spatial resolution within 20-60 s. Because of the ultra-short echo and repetition times, filling of the vascular lumen with gadolinium is depicted; the latter is relatively independent of the complex flow effects on which conventional MRA is based. MRA typical flow voids caused by turbulence or slow flow are thus significantly reduced and allow more reliable depiction of stenoses. After implementing the sequences on our scanner, we evaluated the potential of USTE-MRA for the delineation of various vascular territories in 56 patients. A total of 70 vascular territories were depicted and evaluated by two independent radiologists for image quality and obscuring the arteries because of the contrast of veins. Out of the 56 (4%) diagnostic angiographic quality could not be obtained in only 2 cases. In 13 patients (23%) the studies were judged suboptimal, but diagnostic. In only 3 cases (5%) was venous filling judged to obscure the arteries completely on MIPs (maximum intensity reconstructions), although the studies were diagnostic when evaluated with MRPs (multiplanar reconstructions). Venous superimposition occurred significantly more frequently in the neck than else-where. The greatest improvement over conventional MRA was obtained in the abdomen and thorax where USTE-MRAs can be obtained within a breath-hold without motional artifact.

Effects of partial volume and phase shift between fat and water in gradient-echo magnetic resonance-mammography.

The signal modulations caused by partial volume effect and phase shift between fat and water signal in gradient-echo magnetic resonance mammography (GRE MR-mammography) have been calculated. Based on this, the theoretical sensitivity and specificity of GRE MR-mammography has been investigated considering different evaluation methods for the gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA)-based signal enhancement. The results show that both in- and out-of-phase sequences suffer from partial volume effects in voxels that contain both fat and water. This can decrease sensitivity to Gd-DTPA uptake in small, fat-embedded lesions or in pathology that contains fat interspersed histologically. Additionally, out-of-phase sequences can suffer from phase cancellation effects that can further decrease their sensitivity to Gd-DTPA uptake. In the worst case signal can actually decrease during Gd-DTPA influx. Determination of enhancement relative to the baseline value can decrease the specificity of GRE MR-mammography in the out-of-phase condition and decrease the sensitivity in the in-phase condition. These effects are less pronounced when enhancement is calculated relative to fat. These effects need to be understood since Gd-DTPA uptake is the prime indicator of malignancy in MR-mammography.

CT and MRI findings with pathological correlation of an intracerebral malignant fibrous histiocytoma (MFH): a case report.

The CT and MRI findings in a case of an intracranial malignant fibrous histiocytoma are reported. Pathological correlation was demonstrated and tumour vascularization was best seen at angiography. Despite its low incidence in brain, MFH is of special interest because of its ubiquitous location and poor prognosis.

[Fast and ultra-fast magnetic resonance tomography. Basic principles, pulse sequences and special properties]. / Schnelle und ultraschnelle Magnetresonanztomographie. Grundprinzipien, Pulssequenzen und spezielle Eigenschaften.

The aim of this article is the systematic treatment of fast and ultrafast magnetic resonance imaging (MRI) techniques. Based on the basic principles of signal generation and spatial encoding with magnetic field gradients the differences and important similarities of pulse sequences will be explained. We suggest to replace the conventional grouping of pulse sequences in gradient and spin-echo sequences through single and multi-echo sequences, since the latter is more precise and helpful. We illustrate how single-echo sequences such as "spin-echo", FLASH, FISP, PSIF, CISS and DESS can be derived from a single gradient echo and how multi-echo sequences such as turbo spin-echo RARE, HASTE and GRASE are based on echo-planar imaging. The different properties, advantages and disadvantages of the various sequences will be discussed and frequently used acronyms will be explained.

[Use of ultra-fast computerized tomography in diagnosis of coronary heart disease]. / Einsatz der ultraschnellen Computertomographie in der Diagnostik der koronaren Herzerkrankung.

Ultrafast or electron beam tomography (EBT) permits acquisition of images in 50-100 ms. An artifact-reduced display of heart and vessel structures as well as calcifications can be achieved. Therefore, EBT can be used for the detection and quantification of coronary artery calcification. Thirty-two patients with known coronary artery disease (CAD) were studied by EBT with and without i.v. contrast enhancement and with conventional coronary angiography. Different scoring systems were applied in order to define the basis to compare the data. The results showed a high EBT sensitivity for detection of coronary artery stenosis of up to 94% but low specificity with a maximum of 75%, depending on the scoring system applied. With EBT, differentiation between significant CAD (> 75%) and low-grade CAD (0-75%) showed significant results. The scoring system is not yet completely satisfactory, and with the integration of other screening tests and continuous development of scoring systems, the significance and reliability of this method in evaluation of CAD are expected to increase.