Controlling diffusion of 3He by buffer gases: a structural contrast agent in lung MRI.

PURPOSE: To study the influence of admixing inert buffer gases to laser-polarized (3)He in terms of resulting diffusion coefficients and the consequences for image contrast and resolution. MATERIALS AND METHODS: The diffusion coefficient of (3)He was altered by admixing buffer gases of various molecular weights ((4)He, N(2), and SF(6)). The influence of the pulse sequence and the diffusion coefficient on the appearance of MRI of (laser-polarized) gases was analyzed by comparison of basic theoretical concepts with demonstrative experiments. RESULTS: Excellent agreement between theoretical description and observed signal in simple gradient echoes was observed. A maximum signal gain can be predicted and was experimentally validated. Images acquired under such conditions revealed improved resolution. The nature and concentration of the admixed gas defines a structural threshold for the observed apparent diffusion coefficient (ADC) as demonstrated with diffusion-weighted MRI on a pig's lung flooded with suitable gas mixtures. CONCLUSION: A novel procedure is proposed to control the diffusion coefficient of gases in MRI by admixture of inert buffer gases. Their molecular mass and concentration enter as additional parameters into the equations that describe structural contrast. This allows for setting a structural threshold up to which structures contribute to the image. For MRI of the lung this enables images of very small structural elements (alveoli) only, or in the other extreme, all airways can be displayed with minimal signal loss due to diffusion.

Hemodynamic effects of monomeric nonionic contrast media in pulmonary angiography in chronic thromboembolic pulmonary hypertension.

OBJECTIVE: The purpose of this study was to investigate the hemodynamic safety of the monomeric nonionic contrast agent iomeprol for selective pulmonary angiography in chronic thromboembolic pulmonary hypertension (CTPH), and to investigate the effect of periinterventional oxygen administration. SUBJECTS AND METHODS: Selective pulmonary digital subtraction angiography was performed in 94 patients with CTPH using six bolus injections of iomeprol (posteroanterior, oblique, and lateral projections; both pulmonary arteries; iomeprol, 25 mL at 13 mL/s). Hemodynamics were obtained with Swan-Ganz catheters, and systolic pulmonary artery pressure (PAsyst) was classified into one of three groups: 30 mm Hg or less (control group), greater than 30 but less than or equal to 60 mm Hg (group 1, moderate pulmonary hypertension), and greater than 60 mm Hg (group 2, severe pulmonary hypertension). RESULTS: At baseline, values for PAsyst were 21.4 +/- 2.3 (control group, n = 8), 49.8+/- 8.5 (group 1, n = 18), and 86.5 +/- 18.9 (group 2, n = 68) mm Hg (p < 0.001). Pulmonary vascular resistance indexes (PVRI) were 222 +/- 105 (control), 703 +/- 364 (group 1), and 1,582 +/- 562 (group 2) dyne x s x cm(-5) x m2 (p < 0.001). The mean cardiac indexes were 3.1 (control), 2.8 (group 1), and 2.3 (group 2) L/min/m2 (p < 0.05). Pulmonary capillary wedge pressure (PCw) indicated healthy left heart function. Periinterventional oxygen inhalation improved oxygen saturation in all groups and slightly reduced pulmonary artery pressure and heart rate. Online measurement of pulmonary artery pressure during contrast bolus injection for angiography showed only a minor increase, predominantly in severe pulmonary hypertension (triangle up [difference] PAsyst: 1.3 +/- 1.9 [control], 2.9 +/- 3.4 [group 1], and 3.8 +/- 4.5 [group 2] mm Hg [p < 0.001]). After completion of angiography, right atrial pressure (RAP) and PAsyst were moderately increased: triangle up RAP: 1.4 (control), 2.6 (group 1, p < 0.001), and 3.0 (group 2, p < 0.001) mm Hg; triangle up PAsyst: 3.2 (control), 7.7 (group 1, p < 0.01), and 8.5 (group 2) mm Hg (p < 0.001). PVRI was significantly higher in group 2 (triangle up PVRI: 188 dyne x s x cm(-5) x m2, p < 0.001). CONCLUSION: Selective pulmonary angiography using iomeprol is safe without critical pressure peaks during selective contrast bolus injection or significant hemodynamic derangement in severe CTPH. Periinterventional oxygen inhalation improved pulmonary circulation.

Dynamic MR imaging of breast lesions: correlation with microvessel distribution pattern and histologic characteristics of prognosis.

PURPOSE: To evaluate the association of dynamic enhancement parameters of benign and malignant breast lesions at magnetic resonance (MR) imaging with microvessel distribution and histologic prognostic tumor characteristics. MATERIALS AND METHODS: Regional review board approval and informed consent were obtained. Surgical resection specimens of breast lesions (32 benign, 86 malignant) in 118 patients (age range, 28-86 years; mean, 58 years) who had undergone dynamic T1-weighted MR imaging of both breasts were included in the study. Different MR enhancement parameters and microvessel density (MVD) distribution were determined. In malignant lesions, TNM stage, tumor grade, proliferative activity, and hormone receptor expression were determined. Spearman correlation coefficients; Wilcoxon, Fisher exact, Kruskal Wallis, and chi(2) tests; and logistic regression analysis were used for evaluation. RESULTS: Malignant lesions exhibited a higher ratio of microvessels in tumor periphery versus tumor center than did benign lesions (P < .0005). High vessel ratios (P = .001) and low central vessel numbers (P = .007) were associated with high tumor grade. In malignant lesions, initial enhancement ratios of periphery to center of lesion correlated with the corresponding microvessel ratios (r = 0.61). Yet, a high peripheral MVD was not associated with strong peripheral enhancement (r = -0.09). High enhancement ratios, washout rates, and early enhancement peaks were associated with unfavorable, albeit not significant, prognostic indicators. Visible rim enhancement was the most accurate prognostic enhancement criterion for estrogen receptor status (P = .007), tumor grade (P = .06), and lymph node status (P = .046). Washout was the best discriminating criterion for proliferative activity. CONCLUSION: The different enhancement behaviors of malignant and benign breast lesions cannot be explained by MVD alone; however, a low MVD in the center of carcinoma is reflected quantitatively by a high enhancement ratio and qualitatively by rim enhancement, with an implication of adverse prognosis.

MRI versus helical CT for endoleak detection after endovascular aneurysm repair.

OBJECTIVE: The objective of our study was to investigate the diagnostic accuracy of MRI and helical CT for endoleak detection. SUBJECTS AND METHODS: Fifty-two patients underwent endovascular aneurysm repair with nitinol stent-grafts. Follow-up data sets included contrast-enhanced biphasic CT and MRI within 48 hr after the intervention; at 3, 6, and 12 months; and yearly thereafter. The endoleak size was categorized as < or = 3%, > 3% < or = 10%, > 10% < or = 30%, or > 30% of the maximum cross-sectional aneurysm area. A consensus interpretation of CT and MRI was defined as the standard of reference. RESULTS: Of 252 data sets, 141 showed evidence for endoleaks. The incidence of types I, II, and III endoleaks and complex endoleaks was 3.2%, 40.1%, 8.7%, and 4.0%, respectively. The sensitivity for endoleak detection was 92.9%, 44.0%, 34.8%, and 38.3% for MRI, biphasic CT, uniphasic arterial CT, and uniphasic late CT, respectively. The corresponding negative predictive values were 91.7%, 58.4%, 54.7%, and 56.1%, respectively. The overall accuracy of endoleak detection and correct sizing was 95.2%, 58.3%, 55.6%, and 57.1% for MRI, biphasic CT, uniphasic arterial CT, and uniphasic late CT, respectively. CONCLUSION: MRI is significantly superior to biphasic CT for endoleak detection and rating of endoleak size, followed by uniphasic late and uniphasic arterial CT scans. MRI shows a significant number of endoleaks in cases with negative CT findings and may help illuminate the phenomenon of endotension. Endoleak rates reported after endovascular aneurysm repair substantially depend on the imaging techniques used.

[Hyperpolarized (3)helium gas for functional magnetic resonance imaging of the lung]. / Funktionelle MRT der Lunge unter Verwendung von hyperpolarisiertem 3Helium-Gas.

Lung imaging is traditionally done using X-ray-based methods, since MRI is limited by low proton density as well as inherent magnetic field inhomogeneities of the lung tissue. After introduction of MRI using hyperpolarized noble gases, a totally new field of MRI of the chest has rapidly evolved. These techniques reveal new functional information of the lungs, which could not be obtained before. The first part of this review describes the underlying MR technology explaining distribution of static ventilation, dynamic distribution of ventilation, lung microstructure (apparent diffusion coefficient [ADC]), measurement of oxygen partial pressure (pO(2)), and safety. The clinical potential is afterwards demonstrated in the second part. Therefore, the effort in normal lungs and the mainly focused diseases chronic obstructive pulmonary disease (COPD), smoker's lung, cystic fibrosis, asthma, lung transplantation, and pulmonary embolism are reported.

Local staging of rectal carcinoma and assessment of the circumferential resection margin with high-resolution MRI using an integrated parallel acquisition technique.

PURPOSE: To assess the diagnostic accuracy of integrated parallel acquisition technique (iPAT) in local staging of rectal carcinoma in comparison to conventional high-resolution MRI. MATERIALS AND METHODS: A total of 28 patients with a neoplasm of the rectum and 15 control patients underwent MRI of the pelvis. High-resolution images were acquired conventionally and with iPAT using a modified sensitivity encoding (mSENSE). Image quality, signal-to-noise and contrast-to-noise ratios (SNR, CNR), tumor extent, nodal status, and delineation of the circumferential resection margin (CRM) were compared. In 19 patients with a carcinoma, MR findings were correlated with the histopathological diagnosis. Tumor distance to the CRM was matched with resection specimen in 12 cases. RESULTS: The comparison of both MR techniques revealed no clinically relevant differences in tumor staging and delineation of the CRM, though SNR and CNR were significantly lower in mSENSE images. Tumor stage was concordant in 17 of 19 cases compared to histopathology. In four of nine patients with T3 and T4 carcinomas, the histopathological resection margin was < or =2 mm, in five cases MRI predicted a margin of < or =2 mm. CONCLUSION: The application of iPAT in local staging of rectal carcinoma is time-saving and does not degrade diagnostic accuracy. Tumor stage, nodal status, and the CRM can be assessed equally compared to conventional acquisition techniques.

Analysis of discrete and continuous distributions of ventilatory time constants from dynamic computed tomography.

In this study, an algorithm was developed to measure the distribution of pulmonary time constants (TCs) from dynamic computed tomography (CT) data sets during a sudden airway pressure step up. Simulations with synthetic data were performed to test the methodology as well as the influence of experimental noise. Furthermore the algorithm was applied to in vivo data. In five pigs sudden changes in airway pressure were imposed during dynamic CT acquisition in healthy lungs and in a saline lavage ARDS model. The fractional gas content in the imaged slice (FGC) was calculated by density measurements for each CT image. Temporal variations of the FGC were analysed assuming a model with a continuous distribution of exponentially decaying time constants. The simulations proved the feasibility of the method. The influence of experimental noise could be well evaluated. Analysis of the in vivo data showed that in healthy lungs ventilation processes can be more likely characterized by discrete TCs whereas in ARDS lungs continuous distributions of TCs are observed. The temporal behaviour of lung inflation and deflation can be characterized objectively using the described new methodology. This study indicates that continuous distributions of TCs reflect lung ventilation mechanics more accurately compared to discrete TCs.

Assessment of left ventricular function by breath-hold cine MR imaging: Comparison of different steady-state free precession sequences.

PURPOSE: To compare steady-state free precession (SSFP) sequence protocols with different acquisition times (TA) and temporal resolutions (tRes) due to the implementation of a view sharing technique called shared phases for the assessment of left ventricular (LV) function by breath-hold cine magnetic resonance (MR) imaging. MATERIALS AND METHODS: End-diastolic and end-systolic volumes (EDV, ESV) were measured in contiguous short-axis slices with a thickness of 8 mm acquired in 10 healthy male volunteers. The following true fast imaging with steady-state precession (TrueFISP) sequence protocols were compared: protocol A) internal standard of reference, segmented: tRes 34.5 msec, TA 18 beats per slice; protocol B) segmented, shared phases: tRes 34.1 msec, TA 10 beats per slice; and protocol C) real-time, shared phases, parallel acquisition technique: tRes 47.3 msec, TA 24 beats for 12 slices covering the entire left ventricle. RESULTS: Phase sharing leads to a significant decrease in EDV, stroke volume (SV), and ejection fraction (EF) (median difference -7.0 mL [*], -9.6 mL, and -3.4%, respectively, for protocol B; -15.3 mL, -13.3 mL, and -2.4% for protocol C; P = 0.002, *P = 0.021). The observed median difference of real-time EDV and SV estimates is of clinical relevance. Real-time cine MR imaging shows a greater variability of EDV and SV. No relevant differences in ESV were observed. CONCLUSION: The true cine frame duration of both shared phases sequence protocols exceeds the period of isovolumetric contraction (IVCT) of the left ventricle resulting in a systematic and significant underestimation of EDV and consequently SV and EF. SSFP sequence protocol parameters, particularly tRes and use of view sharing techniques, should therefore be known at follow-up examinations in order to be able to assess LV remodeling in patients with heart failure.

Combination of low and high resolution sequences in two orientations for dynamic contrast-enhanced MRI of the breast: more than a compromise.

The purpose was to combine T1-weighted 3D gradient echo sequences at low and high spatial resolution (and short and longer acquisition time, respectively) in two orientations without compromising signal/time curve analysis and to evaluate the incremental value of assessing architectural features in high resolution images in dynamic contrast-enhanced MR mammography. T1-weighted 3D-FLASH sequences in a 1.5-T scanner (512 x 256 pixel matrix at high resolution; 256 x 128 pixels at low resolution sequences, 72 slices, 1.7-mm slice thickness, TR 8.8 ms, TE 4.5 ms, flip angle 25 degrees) were acquired in a special order during a single investigation. Three observers evaluated architectural features of 36 histopathologically proven lesions using high or low resolution images independently. Architectural features of each lesion were assessed by rating on two three-point scales. Kappa statistics verified the decrease of inter-observer variability. All observers improved assessment of architectural features regarding high resolution images in transversal and coronal orientation (observer A: eight positive, three negative corrections; B: 12/5; C: 16/4). Most positive corrections resulted from improved detection of morphologic criteria of malignancy. Mean inter-observer agreement significantly (P<0.05) increased from "slight" to "moderate" (mean weighted kappa increased from 0.185 to 0.422). This protocol at the charge of slightly enlarged time for measurement offers an elegant way to improve analysis of architectural features in MRM.

Chronic thromboembolic pulmonary hypertension: pre- and postoperative assessment with breath-hold MR imaging techniques.

PURPOSE: To evaluate the potential of breath-hold magnetic resonance (MR) imaging techniques in morphologic and functional assessment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after surgery. MATERIALS AND METHODS: Thirty-four patients with CTEPH were examined before and after pulmonary thromboendarterectomy (PTE). For morphologic assessment, contrast material-enhanced MR angiography was used; for assessment of hemodynamics, velocity-encoded gradient-echo sequences and cine gradient-echo sequences along the short axis of the heart were performed. Contrast-enhanced MR angiography was compared with selective digital subtraction angiography (DSA) for depiction of central thromboembolic material and visualization of the pulmonary arterial tree. Functional analysis included calculation of left and right ventricular ejection fractions and peak velocities, net forward volumes per heartbeat, and blood volume per minute in the left and right pulmonary arteries and ascending aorta. Flow measurements were compared with invasively measured mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR) measurements. Nonparametric Wilcoxon and sign tests were used for statistical analysis. RESULTS: MR angiography revealed typical findings of CTEPH (intraluminal webs and bands, vessel cutoffs, and organized central thromboemboli) in all patients. It depicted pulmonary vessels up to the segmental level in all cases. For subsegmental arteries, DSA revealed significantly more patent vessel segments than did MR angiography (733 versus 681 segments, P <.001). MR angiography revealed technical success of surgery in 33 of 34 patients. Patients had reduced right ventricular ejection fractions and pulmonary peak velocities that significantly increased after PTE (P <.001 for both). Right ventricular ejection fraction had good correlation with PVR (r = 0.6) and MPAP (r = 0.7). The postoperative decrease in MPAP correlated well with the increase in right ventricular ejection fraction (r = 0.8). Postoperatively, there was complete reduction of a preoperatively existing bronchosystemic shunt volume in 33 of 34 patients. CONCLUSION: Breath-hold MR imaging techniques enable morphologic and semiquantitative functional assessment of patients with CTEPH.

Influence of contrast agent dose and image acquisition timing on the quantitative determination of nonviable myocardial tissue using delayed contrast-enhanced magnetic resonance imaging.

BACKGROUND: Delayed contrast-enhanced magnetic resonance imaging (ceMRI) has been shown to identify areas of irreversible myocardial injury due to infarction (MI) with high spatial resolution, allowing precise quantification of nonviable (hyperenhanced) myocardium. The aim of our study was to investigate the size of nonviable myocardium quantitatively as a function of time post-contrast when inversion time is held constant in patients post-myocardial infarction using two contrast agent (CA) doses. METHODS: Nine patients with chronic MI underwent two MR scans on a 1.5 Tesla system. Contrast-enhanced MRI data in two short-axis (SA) slices were continuously acquired until 40 minutes after CA injection [gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), 0.1 mmol/kg body weight = single dose] interrupted only for a complete stack of SA slices encompassing the entire left ventricle (LV) between minutes 20 and 28. Left ventricular mass showing hyperenhancement was determined. The measurement was repeated on the subsequent day with double dose CA (0.2 mmol/kg body weight). Differences of signal intensities for hyperenhanced, nonhyperenhanced myocardium, and LV cavity were calculated. RESULTS: Total mass of hyperenhancement from a complete SA stack acquired between minutes 20 and 28 was lower for single dose CA [9.0% vs. 14.2% for single and double dose, respectively (p = 0.03)]. Ten to 18 minutes after CA injection, there was no significant difference between the two doses and to an internal reference for both single and double dose. For single dose the image contrast between hyperenhancement and LV cavity was superior (minutes 10 to 16, p < 0.05) but inferior between hyperenhanced and nonhyperenhanced myocardium (minutes 6 to 16, p < 0.05). CONCLUSION: Myocardial infarct size measurements are a function of time postcontrast when inversion time is held constant regardless of the contrast agent dose. These data underscore the fact that a standardized imaging protocol that defines how the appropriate inversion time should be selected is needed for comparison of results obtained at various cMR sites.

Assessment of chronic aortic dissection: contribution of different ECG-gated breath-hold MRI techniques.

OBJECTIVE: Our objective was to evaluate the impact of different rapid MRI techniques for the assessment and follow-up of chronic aortic dissections. MATERIALS AND METHODS: Fifty-three patients (41 postoperative Stanford type A, 12 type B dissections) were scanned at 1.5 T during a 3-year period. The study reviewed ECG-gated breath-hold black blood sequences and 3D contrast-enhanced MR angiography of the thoracic aorta supplemented by segmented cine and phase-contrast imaging as well as abdominal contrast-enhanced MR angiography. A retrospective separate analysis of black blood acquisitions and contrast-enhanced MR angiograms from a total of 72 examinations was performed by two radiologists to evaluate detection of intimal flaps and assess image quality. RESULTS: Sensitivity and specificity of black blood sequences compared with those of contrast-enhanced MR angiography in detecting intimal flaps were 87% and 94% for the thoracic aorta, and 54% and 97% for the supraaortic branches, respectively. Contrast-enhanced MR angiography was subjectively rated as superior to black blood techniques for visualizing intimal flaps and yielded better overall image quality (p < 0.001). Aortic valve competence can be assessed on segmented cine techniques. Phase-contrast sequences enabled the quantification of regurgitant flow across the aortic valve and the analysis of flow patterns in the true and false channels. CONCLUSION: Contrast-enhanced MR angiography is superior to black blood MRI in detecting the presence or absence of intimal flaps and is particularly useful in assessing supraaortic branch vessel involvement. Cine and phase-contrast techniques should be included in the imaging follow-up to diagnose possible complications of chronic aortic dissections.

(3)He-MRI in follow-up of lung transplant recipients.

The aim of this study was to evaluate the possible contribution of (3)He-MRI to detect obliterative bronchiolitis (OB) in the follow-up of lung transplant recipients. Nine single- and double-lung transplanted patients were studied by an initial and a follow-up (3)He-MRI study. Images were evaluated subjectively by estimation of ventilation defect area and quantitatively by individually adapted threshold segmentation and subsequent calculation of ventilated lung volume. Bronchiolitis obliterans syndrome (BOS) was diagnosed using pulmonary function tests. At (3)He-MRI, OB was suspected if ventilated lung volume had decreased by 10% or more at the follow-up MRI study compared with the initial study. General accordance between pulmonary function testing and (3)He-MRI was good, although subjective evaluation of (3)He-MRI underestimated improvement in ventilation as obtained by pulmonary function tests. The (3)He-MRI indicated OB in 6 cases. According to pulmonary function tests, BOS was diagnosed in 5 cases. All diagnoses of BOS were also detected by (3)He-MRI. In 2 of these 5 cases, (3)He-MRI indicated OB earlier than pulmonary function tests. The results support the hypothesis that (3)He-MRI may be sensitive for early detection of OB and emphasize the need for larger prospective follow-up studies.

Diagnostic value of routine clinical parameters in acute myocardial infarction: a comparison to delayed contrast enhanced magnetic resonance imaging. Delayed enhancement and routine clinical parameters after myocardial infarction.

AIMS: Contrast enhanced magnetic resonance imaging (ceMRI) has been shown to reliably identify irreversible myocardial injury. The aim of this study was to compare the findings on ceMRI with routine clinical markers of myocardial injury in patients with acute myocardial infarction (MI). METHODS AND RESULTS: Twenty-four patients with acute MI were investigated at 1.5 T. The global myocardial function was analysed with a standard cine MR protocol and a stack of short axis slices encompassing the entire left ventricle. Corresponding short axis slices were acquired for delayed ceMRI 15-20 min after the administration of 0.2 mmol gadolinium-DTPA/kg body weight. Mass of hyperenhancement and peak creatine kinase release (peak CK) was determined for each patient. The presenting 12-lead ECG was analysed for ST-elevation on admission and later development of Q-waves. Mass of hyperenhancement correlated moderately well to peak CK (r = 0.65, p < 0.01) and endsystolic volume index (r = 0.55, p < 0.01). Mass of hyperenhancement was inversely correlated to ejection fraction (r = -0.50, p = 0.02). Neither the presence of ST elevation on the admission ECG nor the later development of Q-waves did relate to the transmural extent of hyperenhancement and to the mass of hyperenhancement. CONCLUSION: Mass of hyperenhancement significantly correlates to global myocardial function and to peak CK. However, there is no relationship between the findings in ceMRI and 12-lead ECG abnormalities on admission suggesting an advantage of ceMRI in defining transmural extent and depicting small areas of necrosis.

Switching off HER-2/neu in a tetracycline-controlled mouse tumor model leads to apoptosis and tumor-size-dependent remission.

Overexpression of the receptor tyrosine kinase HER-2/neu is associated with poor prognosis in patients with breast and ovarian cancer. Recent excitement has surrounded the therapeutic effects of HER-2-blocking therapy strategies and has rekindled interest on the molecular mechanisms of HER-2/neu in tumor biology. To study the role of HER-2/neu overexpression in vivo, we used a murine fibroblast cell line (NIH3T3-her2) conditionally expressing human HER-2/neu under control of a tetracycline-responsive promoter. Expression of HER-2 could be down-regulated below detection limit (>625-fold dilution) by exposure of NIH3T3-her2 cells to anhydrotetracycline (ATc). Subcutaneous injection of NIH3T3-her2 cells into nude mice resulted in rapid tumor growth. Mice with mean tumor volumes of 0.2, 0.8, 1.9, and 14.9 cm(3) were treated daily with 10 mg/kg ATc to switch off HER-2/neu expression, producing reductions in tumor size of 100, 98.1, 81.4, and 74.2%, respectively, by 7 days after onset of ATc administration (P = 0.005, Kruskal-Wallis test). Different long-term effects of HER-2 down-regulation were observed when mice with small (0.2 cm(3); n = 7), intermediate (0.8-1.2 cm(3); n = 10) and large (> or =1.9 cm(3); n = 11) tumors received ATc for up to 40 days. Complete remission was observed for 100, 40, and 18% of the small-, intermediate-, and large-sized tumors, respectively (P = 0.003). However, after 20-45 days of ATc administration, recurrent tumor growth was observed for all mice, even in those with previous complete remissions. The time periods for which mean tumor volume could be suppressed to volumes <0.1 cm(3) under ATc administration were 34, 22, 8, and 0 days for tumors with initial volumes of 0.2, 0.8, 1.9 and 14.9 cm(3), respectively (P = 0.005, Kruskal-Wallis test). Interestingly, HER-2 remained below the detection limit in recurrent tumor tissue, suggesting that initially HER-2-dependent tumors switched to HER-2 independence. The "second hits" leading to HER-2-independent tumor growth have not yet been identified. The rapid regression of tumors after down-regulation of HER-2 was explained by two independent mechanisms: (a) a block in cell cycle progression, as evidenced by a decrease in Ki-67 antigen expression from 40% before ATc treatment to 8.3% after 7 days of ATc treatment; and (b) induction of apoptosis as demonstrated by caspase-3 activation and by the terminal deoxynucleotidyltransferase (Tdt)-mediated nick end labeling assay (TUNEL). In conclusion, we have shown that switching off HER-2 may disturb the sensitive balance between cell proliferation and cell death, leading to apoptosis and tumor remission. Tumor remission was dependent on the volume of the tumors before down-regulation of HER-2/neu.

Systemic pulsatile pressure in type II endoleaks after stent grafting of experimental abdominal aortic aneurysms.

PURPOSE: To investigate pressure and maximum rate of rise of systolic pressure (peak dP/dt) in completely excluded aneurysms and endoleaks to determine the hemodynamic impact of endoleaks. METHODS: In mongrel dogs (n = 36) experimental aneurysms were created by insertion of a patch (portion of rectus abdominis muscle sheath) into the infrarenal aorta. In group I (n = 18), all aortic branches of the aneurysm were ligated and all aneurysms were completely excluded by stent grafts. Group II (n = 18) consisted of aneurysms with patent aortic side branches that represented sources of endoleaks. One week (n = 12), six weeks (n = 12), and six months (n = 12) after stent grafting, hemodynamic measurements were obtained in thrombosed aneurysms and proved endoleaks. Systemic blood pressure and intraaneurysmal pressure were simultaneously measured and the respective peak dP/dt were computed. RESULTS: At the six-month follow-up, the systolic-pressure ratio (intraaneurysmatic pressure: systemic pressure) was significantly increased in endoleaks compared to non-perfused areas (0.879 +/- 0.042 versus 0.438 +/- 0.176, p < 0.01, group II) or completely excluded aneurysms (0.385 +/- 0.221, group I). Peak dP/dt ratio (intraaneurysmal peak dP/dt: systemic peak dP/dt) was 0.922 +/- 0.154 in endoleaks, compared to 0.084 +/- 0.080 in non-perfused areas (group II, p < 0.01), and was 0.146 +/- 0.121 in completely excluded aneurysms (group I). The diastolic-pressure ratio was also increased in endoleaks compared to non-perfused areas (0.929 +/- 0.088 versus 0.655 +/- 0.231, p < 0.01, group II) or completely excluded aneurysms (0.641 +/- 0.278, group I). In excluded aneurysms, pressure exposure declined as the length of the follow-up period increased. CONCLUSION: Type II endoleaks transmit pulsatile pressure of near systemic level and indicate insufficient treatment result. In contrast, complete endovascular exclusion of aneurysms results in significantly reduced pressure exposure.

Measurements of alveolar pO2 using 19F-MRI in partial liquid ventilation.

RATIONALE AND OBJECTIVES: Partial liquid ventilation using Perfluorcarbon (PFC) is an innovative treatment of acute respiratory distress syndrome. However, the underlying mechanisms are not totally clear. The aim was to investigate the distribution of oxygen partial pressure within the PFC-filled lung (ppO2). METHODS: Nine pigs underwent partial liquid ventilation, receiving 20 mL PFC/kg bodyweight (bw). Measurements were obtained by a chemical shift selective TurboFLASH sequence at different axial lung levels. ppO2 was calculated from 19F-MRI by nonlinear curve T1-fitting technique after noise correction. RESULTS: Quantification and distribution of ppO2 was performed successfully. A narrow relationship of the inspiratory O2 fraction and ppO2, as well as a significant ventral-to-dorsal gradient of ppO2 (ventral:dependent lung = 1.9:1) were detected in all subjects and slice positions. CONCLUSIONS: In vivo measurement of local ppO2 gains new and clinical important insights into the physiology of PLV. The previously unknown ppO2 gradient within PFC fits to distribution of perfusion. Dependent lung regions appear to have limited access to O2 from central airways.

Distribution of ventilation in lung transplant recipients: evaluation by dynamic 3He-MRI with lung motion correction.

RATIONALE AND OBJECTIVES: The ability of motion corrected dynamic 3He-magnetic resonance imaging (MRI) to discriminate distributional patterns of inhaled hyperpolarized 3He between different groups of lung transplant recipients was evaluated. METHODS: An ultrafast low-angle shot 2D sequence (temporal resolution 128 ms) was used for ventilation 3He-MRI of 11 single and 6 double lung transplant recipients. After digital motion correction, signal kinetics were evaluated in a tracheal and 7 pulmonary regions of interest. Results from grafts and native lungs as well as from normal and rejected grafts were compared with each other and to reference values from healthy subjects. RESULTS: In emphysema patients, median alveolar rise time, a parameter for increase of alveolar signal, was 0.28 seconds for the graft and 0.48 seconds for the native lung, in fibrosis patients its median was 0.46 seconds for the graft and 0.21 seconds for the native lung. In double lung recipients, alveolar rise time was 0.29 seconds in normal and clinically rejected grafts. CONCLUSIONS: Dynamic ventilation 3He-MRI discriminated normal lung grafts from diseased native lungs in single lung recipients. Graft rejection in double lung recipients could not be discriminated.

Outcome analysis and rational management of enhancing lesions incidentally detected on contrast-enhanced MRI of the breast.

OBJECTIVE: The purpose of our study was to assess the prevalence, characteristics, and clinical consequence of incidentally detected enhancing lesions on MRI of the breast. SUBJECTS AND METHODS. MRI of the breast (1.0-T scanner, dynamic gadolinium-enhanced T1-weighted three-dimensional gradient-echo sequence, double breast coil) was performed on 1273 women for different indications. Enhancing incidental lesions were defined as enhancing lesions on MRIs that were not expected from findings on the previous conventional imaging. They were classified in five assessment categories using a scoring system based on morphologic and kinetic enhancement characteristics. Detection of enhancing incidental lesions resulted in a review of mammograms and sonograms with the aim of also localizing these lesions on conventional imaging. The lesions were either biopsied or followed up. RESULTS: Twenty-five percent (274/1086) of all enhancing lesions detected in the study population were enhancing incidental lesions. Enhancing incidental lesions were found in 16% (210/1273) of all study patients. Forty-one percent (113/274) of the enhancing incidental lesions were histologically confirmed. Forty-eight percent (54/113) of the biopsied and 20% (54/274) of all enhancing incidental lesions were malignant. Eleven percent (54/508) of all malignant lesions occurring in the 1273 women were detected solely through additional MRI. Fifty-seven percent (31/54) of these MRI-detected malignant lesions could be identified on a reevaluation of sonograms and mammograms. CONCLUSION: Detection of enhancing incidental lesions should lead to a thorough reevaluation of mammograms and sonograms. If not reidentified, suspicious enhancing incidental lesions should be biopsied, and enhancing incidental lesions that are probably benign should be carefully followed up. Indeterminate enhancing incidental lesions should be histologically examined by minimally invasive techniques or, if they are small, followed up by another MRI 6 months later.

No influence of magnetic fields on cell cycle progression using conditions relevant for patients during MRI.

The purpose of this study was to examine whether exposure to magnetic fields (MFs) relevant for magnetic resonance imaging (MRI) in clinical routine influences cell cycle progression in two tumor cell lines in vitro. HL60 and EA2 cells were exposed to four types of MFs: (i) static MF of 1.5 and 7.05 T, (ii) extremely low frequency magnetic gradient fields (ELFMGFs) with +/- 10 mT/m and 100 Hz, as well as +/- 100 mT/m and 100 Hz, (iii) pulsed high frequency MF in the radiofrequency (RF) range (63.6 MHz, 5.8 microT), and (iv) a combination of (i-iii). Exposure periods ranged from 1 to 24 h. Cell cycle distribution (G(0)/G(1), S, and G(2)/M phases) was analyzed by flow cytometry. Cell cycle analysis did not reveal differences between the exposed and the control cells. As expected, positive controls with irradiated (8 Gy) HL60 and EA2 cells showed a strong G(2)/M arrest. Using conditions that are relevant for patients during MRI, no influence of MFs on cell cycle progression was observed in these cell lines. Care was taken to control secondary parameters of influence, such as vibration by the MR scanner or temperature to avoid false positive results.