MR-guided interstitial laser-induced thermotherapy of hepatic metastasis combined with arterial blood flow reduction: technique and first clinical results in an open MR system.

The feasibility and safety of percutaneous laser-induced thermotherapy (LITT) of liver metastases in an open low-field magnetic resonance imaging (MRI) system combined with microsphere-modulated blood flow reduction were tested. Nd:YAG laser therapy with an internally cooled laser applicator was performed under local anesthesia on 20 patients with 34 liver metastases. To increase the effectiveness of LITT, degradable starch microspheres were injected into the proper hepatic artery through an MR-visible catheter initially inserted under fluoroscopy. Near real-time imaging was used for positioning the laser applicator. A T1-weighted gradient-echo breath-hold sequence was used for catheter localization and temperature monitoring. The volumes of the liver metastases and the thermonecroses were determined. MRI-guided LITT could be performed in all patients with no clinically relevant complications. Intraprocedural imaging underestimated the extent of thermonecrosis. In conclusion, percutaneous LITT of liver metastases after injection of starch microspheres is both technically feasible and safe in an open MRI system. J. Magn. Reson. Imaging 2001;13:31-36.

[Laser-induced thermotherapy (LITT) for liver metastasis in an open 0.2T MRI]. / Laserinduzierte Thermotherapie (LITT) von Lebermetastasen in einem offenen 0,2T MRT.

OBJECTIVE: To test the feasibility and safety of the laser-induced thermotherapy (LITT) for liver metastases in open MR imaging system operating at 0.2 Tesla. METHOD: Laser therapy using the Nd:YAG laser was performed on 25 patients with a total of 41 liver metastases. An open low-field MRI scanner was used for puncture, positioning of the laser applicator, and monitoring the therapy. A true FISP sequence was used to track the puncture in close to real-time. Localization diagnostics and temperature monitoring were aided by T1-weighted gradient echo sequences in the breath-holding technique. In the first follow up after 24-48 hours, a contrast-enhanced T1-weighted gradient-echo sequence was performed in an MRI scanner at 1.5T. The pre-, intra- and postinterventional volumes of the liver metastases as well as the thermolesions and the thermonecroses were determined. RESULTS: LITT in an open MRI system was technically feasible in all patients with no clinically relevant complications. The mean volumes of the thermolesions measured during intervention in low-field MRI were lower than the volumes of the thermonecroses measured after intervention in high-field MRI. CONCLUSION: The technique presented here of laser-induced thermotherapy for liver metastases in an open MRI system is technically feasible and safe.

Laser-induced thermotherapy for the treatment of liver metastasis. Correlation of gadolinium-DTPA-enhanced MRI with histomorphologic findings to determine criteria for follow-up monitoring.

PURPOSE: To evaluate gadolinium (Gd)-diethylenetriamine-pentaacetic-acid (DTPA)-enhanced magnetic resonance imaging (MRI) for follow-up monitoring of laser-induced thermotherapy (LITT) and to determine a useful examination schedule. METHODS: LITT of the liver was performed in 55 rabbits using a neodymium: yttrium-aluminum-garnet (Nd:YAG) laser (4-W power output, 840-s exposure time). Gd-DTPA MRI and histologic examinations were performed at different times (0-168 days). RESULTS: Laser-induced lesions underwent regeneration and volume size reduction (69% after 168 days). The correlation coefficient (MR vs. macroscopic analysis) for the mean lesion diameter was r = 0.96. Histology of lesions comprised the four zones that correlated best with MRI findings. Coagulation necroses immediately after LITT was seen as an area of no enhancement on Gd-DTPA MRI. Circular enhancement was first seen 72-96 h after LITT, which was due to early mesenchymal proliferation. CONCLUSIONS: Gd-DTPA MRI is a good monitoring procedure for LITT. MRI should be performed 24 and 96 h after LITT.

Vascular lesions in children: percutaneous MR imaging-guided interstitial Nd:YAG laser therapy--preliminary experience.

PURPOSE: To investigate the use of magnetic resonance (MR) imaging to guide interstitial laser therapy of deep hemangiomas and vascular malformations in children. MATERIALS AND METHODS: Sixteen children aged 3 months to 16 years with symptomatic vascular lesions underwent percutaneous laser treatment. MR imaging guidance of the laser applicator and online thermomonitoring with MR imaging were performed with a 0.2-T open MR system. Follow-up studies were performed 2 days and 6 weeks after thermotherapy. RESULTS: Interactive positioning of the laser applicator was possible in all patients. Online thermomonitoring was possible in 122 of 137 therapy spots (89%). There was a good correlation between volumes of coagulated tissue on intraprocedural T1-weighted images and volumes of coagulated tissue on follow-up T2-weighted images. At 6-week follow-up, MR imaging demonstrated a reduction in lesion size in 10 patients (mean reduction, 72%) and an increase in lesion size in two patients (mean increase, 134%). Clinical symptoms improved in 14 of 16 patients (88%). CONCLUSION: MR imaging-guided laser therapy appears to be a safe and potentially effective minimally invasive treatment for selected children with vascular lesions.

[Electron-beam tomographic imaging of the coronary arteries: an experimental comparison between monomeric and dimeric x-ray contrast media]. / Elektronenstrahltomographische Darstellung der Koronararterien: Experimenteller Vergleich zwischen einem monomeren und einem dimeren Röntgenkontrastmittel.

PURPOSE: Comparison of a monomeric and a dimeric radiographic contrast medium in the visualisation of the coronary arteries via electron beam tomography (EBT). MATERIAL AND METHODS: In a total of 6 Göttingen minipigs the heart was examined by EBT (40 sections, ECG-triggering, 1.5 mm section thickness, 100 ms acquisition time) after injection of both iopamidol (monomer, 370 mg l/ml) and iotrolan (dimer, 320 mg l/ml) at a dose of 740 mg l/kg. Injection rate and scan delay were adjusted to heart rate and circulation time. RESULTS: The intravascular increase in density after intravenous injection of iotrolan was significantly higher and longer than after injection of iopamidol (> 300 HE: 28 +/- 4 versus 17 +/- 5 cardiac cycles; p < 0.05). Iotrolan attained a higher score in the visualisation of the coronary arteries in three-dimensional surface reconstructions (p < 0.05). CONCLUSION: The dimeric contrast medium iotrolan proved superior to the monomeric agent iopamidol for visualisation of the coronary arteries via EBT.

Heat response of HT29 cells depends strongly on perfusion--a 31P NMR spectroscopy, HPLC and cell survival analysis.

A model system of perfused human colon adenocarcinoma cells (HT29) encapsulated in alginate was used to examine metabolic response to heat therapy with 31P NMR spectroscopy, HPLC and cell survival analysis. The presented data show, that perfused (medium flow during hyperthermia) and non-perfused (no medium flow during hyperthermia) cells are very difficult in their sensitivity to hyperthermia. Under equivalent experimental conditions with respect to medium pH, oxygen and nutrient concentration, encapsulated perfused HT 29 cells display a significantly lower thermal sensitivity than non-perfused cells. This reduced sensitivity of perfused cells is characterized by an increased cell survival and relative ATP concentration, and reduced drop of the NTP/Pi ratio in the long-term follow up towards zero. The relative ATP concentration determined by HPLC after hyperthermia is correlated with the clonogenic survival fraction. There is a direct relationship, depending on the specific experimental conditions (perfused, non-perfused). For perfused cells only a slight dependency of survival and relative ATP concentration on heat dose is observed. In consequence, the correlation between survival and relative ATP concentration is weak, described by log(SFperf) = 0.7*[ATP-12.4, R2 = 0.79, p < 0.04. For non-perfused cells the correlation is stronger resulting in a relationship of log(SFno perf) = 0.6*[ATP]-9.0, R2 = 0.98, p < 0.0002. Altogether, the presented data suggest that the relative ATP concentration measured by HPLC after hyperthermia might be predictive for cell survival. On the other hand, a dependence between cell survival and long-term changes of NTP/Pi has been found. The results confirm the importance of tumour perfusion for hyperthermia-induced metabolic changes and cytotoxicity and therefore, for the therapeutic outcome.

[An interstitial miniature antenna for localized in vivo P-31 MR spectroscopy]. / Eine interstitielle Miniaturantenne für die lokalisierte In-vivo-31P-MR-Spektroskopie.

BACKGROUND: Phosphorus spectroscopy can be used to assess response in tumor therapy and to monitor response. An additional response parameter would be useful for individualization in oncological therapy. Methodical problems of localisation and contamination make it more difficult to interpret and reproduce the spectra. Interstitial and endoluminal spectroscopy antennas placed directly within or close to the tumor could provide help in this problem. MATERIAL AND METHOD: We developed an interstitial 31P MRS antenna together with a tuning network which can be used in thermometry catheters for hyperthermia within an internal lumen of 1.1 mm in diameter. A prototype of this type of miniature antenna suitable for use in Siemens MRI scanners at 1.5 T was described spectroscopically with regard to excitation profile, range and SNR. RESULTS: In terms of quality, the excitation profiles of the interstitial antennas in relation to orientation correspond to those of comparable but considerably larger endocavitary antennas and catheter coils for MR imaging and spectroscopy. Maximum sensitivity was achieved by aligning the coil normal perpendicular to the B0 field. Signal losses of up to 50% have to be reckoned with when using other orientations. The maximum range of the interstitial antenna was determined using spectroscopy and was found to be 5 mm, i.e. 9 times coil radius. The sensitivity (SNR, detection sensitivity) of the studied type of interstitial antenna allows in vivo 31P spectroscopy to be performed despite the unusually low axial dimension (coil radius r = 0.55 mm). The prototype of the described interstitial antenna was used to measure an in vivo spectrum from the back muscle of a rabbit in 10 min. Nevertheless, the detection volume of at least some ml necessary for 31P spectroscopy results mainly from the large antenna length. CONCLUSION: The sensitivity (SNR, detection sensitivity) of the interstitial antenna needs to be further improved in order to assess treatment response in patients. However, the construction principle is suitable for intracavitary 31P spectroscopy antenna with larger diameters, which can be used for advanced rectal, cervical and prostate carcinomas.

Magnetic resonance lymphography in rats: effects of muscular activity and hyperthermia on the lymph node uptake of intravenously injected superparamagnetic iron oxide particles.

RATIONALE AND OBJECTIVES: We investigated the influence of muscular activity and regional body temperature changes on the accumulation of intravenously (i.v.) administered, dextran-coated superparamagnetic iron oxide (SPIO) particles in the lymph nodes of rats. METHODS: Four groups of rats (N = 21) were used. Five rats were allowed to move freely after i.v. contrast administration (group 1). In another five rats, muscular inactivity (group 2) was induced during i.v. injection of SPIO particles and for up to 2 hr thereafter by anesthesia. In seven rats (likewise anesthetized), the contrast agent was administered while the extremities of one side of the body were warmed in a water bath for 2 hr (group 3). The rats in groups 1-3 received 100 mumol Fe/kg of the contrast agent. Four rats not given SPIO particles served as the control group (group 4). The lymph nodes of all animals were removed 24 hr after SPIO administration and were embedded in an agar matrix for magnetic resonance imaging at 1.5 T using a proton-density-weighted spin-echo (PD-SE) sequence and a T2*-weighted gradient-recalled echo (T2* GRE) sequence. RESULTS: Signal loss varied widely among the different lymph nodes in group 1. A pronounced signal reduction was observed in the mesenteric (PD-SE = 20 +/- 6%, T2* GRE = 55 +/- 19%), iliac (PD-SE = 13 +/- 13%, T2* GRE = 44 +/- 24%), and popliteal (PD-SE = 24 +/- 7%, T2* GRE = 70 +/- 11%) lymph nodes and only a moderate reduction in the mandibular (PD-SE = 4 +/- 7%, T2* GRE = 42 +/- 15%), axillary (PD-SE = 0 +/- 4%, T2* GRE = 8 +/- 7%), and inguinal (PD-SE = 5 +/- 5%, T2* GRE = 34 +/- 18%) lymph nodes. The least pronounced signal loss occurred in the peripheral lymph nodes of group 2, ranging from 0 +/- 3% for PD-SE sequences and 10 +/- 11% for T2* GRE sequences to 13 +/- 15% for PD-SE sequences and 41 +/- 19% for T2* GRE sequences. In group 3, the uptake of contrast material in the peripheral lymph nodes of the hyperthermal side was significantly more pronounced than on the contralateral side (p < .01), and the contrast agent was distributed more evenly to the different lymph node groups than in group 1. CONCLUSION: Muscular activity and regional hyperthermia markedly influence the accumulation of SPIO particles in different lymph node groups in rats. These findings must be considered in preclinical studies and in the clinical administration of MR lymphography.

Evaluation of gadobutrol in a rabbit model as a new lanthanide contrast agent for computed tomography.

RATIONALE AND OBJECTIVES: The efficacy of the neutral lanthanide contrast agent gadobutrol was compared to that of the iodinated contrast agent iopromide in rabbits. METHODS: The computed tomography (CT) attenuation of increasing concentrations of gadolinium (Gd) (gadobutrol) and iodine (I) (iopromide) was measured in Hounsfield units (HU) in aqueous solution at 80, 120, and 137 kV. The peak enhancement (net increase in CT attenuation compared with baseline) and the time-enhancement product in the aorta and in the renal parenchyma of the outer and inner cortex were measured in rabbits over a 5-minute period after the animals were given single intravenous injections of 0.7, 1.0, and 1.5 mmol Gd/kg of gadobutrol and 1.0 and 2.4 mmol I/kg of iopromide. RESULTS: In vitro, the CT attenuation of gadolinium was 40% higher than that of iodine at equivalent mass concentrations (120 kV). The mean peak enhancements in the aorta after the injections of 0.7, 1.0, and 1.5 mmol Gd/kg and 1.0 and 2.4 mmol I/kg were 216, 313, 591, 224, and 498 HU, respectively. In addition, a 30-second injection of the high dose of gadobutrol resulted in an attenuation profile that was suitable for a three-dimensional reconstruction of the aorta and the renal vasculature. CONCLUSIONS: Because of the higher CT attenuation of gadolinium compared with that of iodine, the neutral macrocyclic chelate gadobutrol is a more effective contrast agent than iopromide for CT at lower doses of the imaging atom.

[Rheumatoid arthritis of the hand. The initial results with 31-phosphorus MR spectroscopy]. / Rheumatoide Arthritis der Hand. Erste Ergebnisse mit der 31Phosphor-MR-Spektroskopie.

The aim of this study was to demonstrate metabolic changes in the small joints of the hand due to rheumatoid arthritis by means of 31-phosphorus spectroscopy. Suitable measurements were developed and 11 normals and 12 patients were then examined during the course of treatment. Relative concentration of low energy phosphorus metabolites was increased in arthritic joints. The phospholipid quotient (phosphomonoester/phosphodiester) and the relationship of inorganic phosphate and beta-nucleoside triphosphate were significant factors during the course of individual treatments.

Magnetic resonance imaging-controlled laser-induced interstitial thermotherapy.

RATIONALE AND OBJECTIVES: Laser-induced interstitial thermotherapy (LITT) may become an attractive modality for minimally invasive tumor therapy. Magnetic resonance imaging (MRI) could be used to assist this procedure. METHODS: A T1-weighted turbo fast low-angle shot (FLASH) sequence for on-line monitoring of the laser-influenced region (liver, muscle) was investigated. Sequence parameters were optimized for maximal image contrast. Magnetic resonance imaging-controlled LITT was performed in vitro, in vivo (rabbits), and in 8 human investigations (6 patients). Special laser applicators were used to establish a uniform laser light distribution. RESULTS: With the MRI sequence used, the LITT region is visualized as a bright area outlined by a dark border. This dark border corresponds to an isotherm of 45 +/- 2 degrees C depending on the sequence parameters used. CONCLUSION: With the T1-weighted turbo-FLASH sequence, MRI can be used for on-line monitoring of interstitial laser-induced thermotherapy in moving organs.

Electron microscopic and 31-P NMR studies of ischemic injured rat livers during preservation and reflow.

Ischemic injury induced during preservation and reperfusion contributes to post-operative failure in liver transplantation. Hepatic injury and recovery from preservation was studied in an isolated rat liver model reperfused with oxygenated erythrocytes. In order to correlate morphological and functional findings, 31-P nuclear magnetic resonance spectroscopy and electron microscopy were used to investigate metabolic and ultrastructural changes during 6 hours of reperfusion. Following cold preservation, EM's showed a primary sinusoidal cell injury, whereas the hepatocytes were well maintained. During reperfusion, hepatocytes displayed further damage. The simultaneous presence of vacuolarly degenerated mitochondria and mitochondria of increased activity was noted. 31-P NMP spectra demonstrated initially a partial ATP-recovery. The maximum level of 60% of the control ATP-value could not be further increased. EM and 31-P NMR indicate that the progressive injury to the liver is due to microcirculatory malfunction induced by an endothelial cell damage, followed by injured hepatocytes themselves, and the consequent intracellular energy crisis that is produced.

Effect of pentoxiphylline on the recovery of the preserved rat liver: 31P NMR and ultrastructural studies.

Hepatic failure often occurs following transplantation. This is primarily due to cold ischemia during preservation, warm ischemia during implantation, and finally reperfusion damage after transplantation and reflow. The possibility that this ischemia and reperfusion-induced damage can be reduced by preischemic application of a xanthine derivative (pentoxiphylline) was examined using 31P NMR spectroscopy and electron microscopy (EM) studies of bioenergetic and ultrastructural changes in oxygenated erythrocyte-perfused rat livers. EM illustrated that the hepatocytes and the mitochondria appeared to be relatively unaffected by cold preservation of the liver, whereas the endothelial cells lining the sinusoids became disrupted. After reperfusion, NMR spectroscopy showed a partial recovery of ATP levels, and EM indicated progressive mitochondrial injury. This progressive injury to the liver was probably due to endothelial cell damage which resulted in microcirculatory malfunction and free radical formation during reperfusion. Pentoxiphylline pretreated livers showed better preservation of the cell morphology and exhibited better ATP recovery than untreated livers. Pentoxiphylline is known to prevent the loss of precursors of ATP resynthesis by inhibiting AMP dephosphorylation during ischemia and improves the microcirculation via vasodilatory properties following ischemia. Thus, it is concluded that pentoxiphylline may ameliorate ischemia-induced cell damage during transplantation.

31P nuclear magnetic resonance spectroscopy, histology and cytokinetics of a xenografted hypopharynx carcinoma following treatment with cisplatin: comparison in three sublines with increasing resistance.

The changes in the phosphorus metabolism of a xenografted hypopharynx carcinoma (Hyp 1), sensitive to cisplatin (CDDP), were compared to those occurring in two sublines of the tumour, characterised by moderate or high resistance to CDDP (Hyp 1/H and Hyp 1/R) following, i.p. administration of 4, 8 or 12 mg CDDP/kg-1. The investigations were performed by in vivo 31P nuclear magnetic resonance (NMR) spectroscopy. Parallel to the NMR experiments, the cytokinetic and histological alterations in the tumours were studied under the same experimental conditions. No mentionable differences in the levels of the main phosphorus-containing metabolites could be detected between the three tumour lines before treatment. Following application of CDDP, the alterations in the NMR spectra were clearly related to the degree of tumour response. The most sensitive and earliest marker of tumour regression was a decrease in the phosphomonoester/phosphodiester ratio, parallelled by a gradual increase in the phosphocreatine/inorganic phosphorus quotient. In the resistant tumour lines Hyp 1/H and Hyp 1/R non-responding tumours showed alterations in the 31P NMR spectrum which were similar to those observed during uninfluenced tumour growth. Marked changes in the 31P NMR spectrum were always associated with severe cytotoxic lesions following therapy. The results suggest that the changes detected by 31P NMR spectroscopy following chemotherapy with CDDP are response-specific.