Changes in oxygenation of intracranial tumors with carbogen: a BOLD MRI and EPR oximetry study

PURPOSE: To examine, using blood oxygen level dependent (BOLD) MRI and EPR oximetry, the changes in oxygenation of intracranial tumors induced by carbogen breathing. MATERIALS AND METHODS: The 9L and CNS-1 intracranial rat tumor models were imaged at 7T, before and during carbogen breathing, using a multi-echo gradient-echo (GE) sequence to map R(2)*. On a different group of 9L tumors, tissue pO(2) was measured using EPR oximetry with lithium phthalocyanine as the oxygen-sensitive material. RESULTS: The average decline in R(2)* with carbogen breathing was 13 +/- 1 s(-1) in the CNS-1 tumors and 29 +/- 4 s(-1) in the 9L tumor. The SI vs. TE decay curves indicate the presence of multiple components in the tumor. Tissue pO(2) in the two 9L tumors measured was 8.6 +/- 0.5 and 3.6 +/- 0.6 mmHg during air breathing, and rose to 20 +/- 7 and 16 +/- 4 mmHg (mean +/- SE) with carbogen breathing. Significant changes were observed by 10 minutes, but changes in pO(2) and R(2)* continued in some subjects over the entire 40 minutes. CONCLUSION: EPR results indicate that glial sarcomas may be radiobiologically hypoxic. Both EPR and BOLD data indicate that carbogen breathing increases brain tumor oxygenation. These data support the use of BOLD imaging to monitor changes in oxygenation in brain tumors.     

Functional characterization of prostate cancer by integrated magnetic resonance imaging and oxygenation changes during carbogen breathing

OBJECTIVE: The objective of this study was to evaluate the changes in oxygenation of prostate cancer induced by carbogen breathing using blood oxygen level-dependent (BOLD) magnetic resonance image (MRI) with an endorectal coil (eMRI). MATERIALS AND METHODS: In 32 patients with biopsy-proven prostate cancer, endorectal MRI was performed at 1.5 Tesla using the BOLD method. Images were acquired during 4 x 4-minute episodes alternating between room air and carbogen (95% O2/5% CO2) breathing. In each episode, 40 images were acquired (T2*-weighted EPI sequence, 12-14 slices, 3-mm thickness). All patients underwent radical prostatectomy; BOLD-MRI findings were correlated with the histopathologic results. RESULTS: BOLD-MRI could be evaluated in 29 patients, and revealed heterogeneous signal changes of normal prostate and cancer tissue similar to the heterogeneity of prostate tissue in anatomic/pathologic preparation. A significant signal intensity increase (P = 0.004) was found in normal central gland and peripheral zone during carbogen breathing. Signal enhancement in carcinoma was significantly lower (P = 0.004) compared with the contralateral normal side. CONCLUSION: Intrinsic blood-tissue contrast-functional MRI during carbogen breathing may help detect and characterize prostate carcinoma from normal tissue, particularly in small 1-sided carcinomas. This may be useful for identifying candidates for radiotherapy and monitoring noninvasive therapeutic approaches.     

Nonnvasive assessment of vascular architecture and function during modulated blood oxygenation using susceptibility weighted magnetic resonance imaging.

Susceptibility weighted imaging (SWI) is a BOLD-sensitive method for visualizing anatomical features such as small cerebral veins in high detail. The purpose of this study was to evaluate high-resolution SWI in combination with a modulation of blood oxygenation by breathing of air, carbogen, and oxygen and to directly visualize the effects of changing blood oxygenation on the magnetic field inside and around venous blood vessels. Signal changes associated with the response to carbogen and oxygen breathing were evaluated in different anatomic regions in healthy volunteers and in two patients with brain tumors. In the magnitude images inhalation of carbogen led to significant signal intensity changes ranging from +4.4 +/- 1.9% to +9.5 +/- 1.4% in gray matter and no significant changes in thalamus, putamen, and white matter. During oxygen breathing mean signal changes were smaller than during carbogen breathing. The method is capable of producing high-resolution functional maps of BOLD response to carbogen and oxygen breathing as well as high-resolution images of venous vasculature. Its sensitivity to changes in blood oxygenation was demonstrated by in vivo visualization of the BOLD effect via phase imaging.     

Radiosensitization of two murine tumours with mild temperature hyperthermia and carbogen breathing.

PURPOSE: To test the individual and combined effects of local mild temperature hyperthermia (MTH) at 41.5 degrees C for 60 min and carbogen breathing on tumour radiosensitivity. MATERIALS AND METHODS: The FSall fibrosarcoma of C3H mice and the SCK mammary carcinoma of A/J mice were used. The effect of various treatments on tumour cell survival was determined using the in vivo/in vitro tumour excision assay, and the radiobiological hypoxic fraction was calculated. The tumour radiation sensitivity was tested with the tumour growth delay assay. RESULTS: The radiobiological hypoxic cell fraction (HF) in control FSall and SCK tumours was 0.45 and 0.78, respectively, and these values decreased to 0.12 in FSall tumours and 0.22 in SCK tumours when determined immediately after the tumours were treated with MTH. The HF was 0.32 in FSall tumours and 0.33 in SCK tumours after carbogen breathing was applied. When tumours were treated with MTH and the animals breathed carbogen the HF decreased to 0.03-0.04 in both FSall and SCK tumours. MTH treatment alone had only a small effect on tumour growth, but MTH treatment applied before irradiating the tumours significantly increased the radiation-induced tumour growth delay. Carbogen breathing modestly improved the radiation-induced tumour growth delay while the combination of MTH treatment and carbogen breathing caused the largest increase in radiation-induced tumour growth delay. CONCLUSIONS: MTH treatment alone and combined with carbogen breathing substantially increased the tumour radiation response probably through an increase in the tumour oxygenation status.     

Radiosensitization of two murine tumours with mild temperature hyperthermia and carbogen breathing

Purpose: To test the individual and combined effects of local mild temperature hyperthermia (MTH) at 41.5 C for 60min and carbogen breathing on tumour radiosensitivity. Materials and methods: The FSall fibrosarcoma of C3H mice and the SCK mammary carcinoma of A/J mice were used. The effect of various treatments on tumour cell survival was determined using the in vivo/in vitro tumour excision assay, and the radiobiological hypoxic fraction was calculated. The tumour radiation sensitivity was tested with the tumour growth delay assay. Results: The radiobiological hypoxic cell fraction (HF) in control FSall and SCK tumours was 0.45 and 0.78, respectively, and these values decreased to 0.12 in FSall tumours and 0.22 in SCK tumours when determined immediately after the tumours were treated with MTH. The HF was 0.32 in FSall tumours and 0.33 in SCK tumours after carbogen breathing was applied. When tumours were treated with MTH and the animals breathed carbogen the HF decreased to 0.03-0.04 in both FSall and SCK tumours. MTH treatment alone had only a small effect on tumour growth, but MTH treatment applied before irradiating the tumours significantly increased the radiation-induced tumour growth delay. Carbogen breathing modestly improved the radiation-induced tumour growth delay while the combination of MTH treatment and carbogen breathing caused the largest increase in radiation-induced tumour growth delay. Conclusions: MTH treatment alone and combined with carbogen breathing substantially increased the tumour radiation response probably through an increase in the tumour oxygenation status.     

In vivo animal functional MRI: improved image quality with a body-adapted mold

PURPOSE: To reduce functional magnetic resonance imaging (fMRI) susceptibility distortion at the air/tissue interphase in animal experiments. MATERIALS AND METHODS: We investigated the applicability of a body-adaptable flexible mold consisting of a fast-setting alginate. This technique was implemented for subcutaneous growing tumors in rats and for the brains of monkeys. RESULTS: The T(2)*-weighted gradient-echo, echo-planar imaging (GE-EPI) data obtained with the body-adapted mold showed a reduction of susceptibility artifacts and improved image quality. With both rat tumor and monkey brain, an optimized match with the anatomical T(1) images was possible. CONCLUSION: The present mold methodology is a rapid, easy, and inexpensive way to reduce magnetic susceptibility during animal GE-EPI.     

BOLD MRI of human tumor oxygenation during carbogen breathing

An MRI method is described for demonstrating improved oxygenation of human tumors and normal tissues during carbogen inhalation (95% O2, 5% CO2). T2*-weighted gradient-echo imaging was performed before, during, and after carbogen breathing in 47 tumor patients and 13 male volunteers. Analysis of artifacts and signal intensity was performed. Thirty-six successful tumor examinations were obtained. Twenty showed significant whole-tumor signal increases (mean 21.0%, range 6.5-82.4%), and one decreased (-26.5 +/- 8.0%). Patterns of signal change were heterogeneous in responding tumors. Five of 13 normal prostate glands (four volunteers and nine patients with nonprostatic tumors) showed significant enhancement (mean 11.4%, range 8.4-14.0%). An increase in brain signal was seen in 11 of 13 assessable patients (mean 8.0 +/- 3.7%, range 5.0-11.7%). T2*-weighted tumor MRI during carbogen breathing is possible in humans. High failure rates occurred due to respiratory distress. Significant enhancement was seen in 56%, suggesting improved tissue oxygenation and blood flow, which could identify these patients as more likely to benefit from carbogen radiosensitization.     

Tumor R2* is a prognostic indicator of acute radiotherapeutic response in rodent tumors

PURPOSE: To test the prognostic potential of tumor R2* with respect to radiotherapeutic outcome. Blood oxygenation level dependent (BOLD) MRI images are sensitive to changes in deoxyhemoglobin concentration through the transverse MRI relaxation rate R2* of tissue water, hence the quantitative measurement of tumor R2* may be related to tissue oxygenation. METHODS AND MATERIALS: Tumor growth inhibition in response to radiation was established for both GH3 prolactinomas and RIF-1 fibrosarcomas with animals breathing either air or carbogen during radiation. In a separate cohort, the baseline R2* and carbogen (95% O2, 5% CO2)-induced DeltaR2* of rat GH3 prolactinomas and murine RIF-1 fibrosarcomas were quantified using multigradient echo (MGRE) MRI prior to radiotherapy, and correlated with subsequent tumor growth inhibition in response to ionizing radiation, while the animals breathed air. RESULTS: A radiation dose of 15 Gy caused pronounced growth delay in both tumor models and transient regression of the GH3 prolactinomas. When the animals breathed carbogen during radiation, the growth delay/regression was enhanced only in the GH3 prolactinomas. The GH3 prolactinomas, which exhibit a relatively fast baseline R2* and large DeltaR2* in response to carbogen breathing prior to radiotherapy, showed a substantial reduction in normalized tumor volume to 66 +/- 3% with air breathing and 36 +/- 5% with carbogen seven days after 15 Gy irradiation. In contrast, the effect of 15 Gy on the RIF-1 fibrosarcomas, which give a relatively slow baseline R2* and negligible DeltaR2* response to carbogen prior to treatment, showed a much smaller growth inhibition (143 +/- 3% with air, 133 +/- 12% with carbogen). CONCLUSION: Quantitation of tumor R2* and carbogen-induced DeltaR2* by MGRE MRI provides completely noninvasive prognostic indicators of a potential acute radiotherapeutic response.     

Rapid tissue oxygen tension mapping using 19F inversion-recovery echo-planar imaging of P erfluoro-15 -crown-5-ether

Fluorine-19 inversion-recovery, echo-planar imaging (IR-EPI) wais used in conjunction with a new PFC emulsion, perfluoro-15-crown-5-ether, to map the spatial distribution of oxygen tension in murine liver, spleen and radiation induced fibrosarcoma (RIF-1) tumors. Intravenously administered PFC emulsions were allowed to sequester in the liver, spleen, and tumor 3 to 7 days prior to imaging experiments. Seven, 64 × 64 IR-EPls were acquired with successively increasing inversion times (TI). A nonlinear least-squares regression algorithm was used to fit the seven two-dimensional matrices, on a pixel-by-pixel basis, to solve for the relaxation rate, R₁, of the sequestered PFC. From in vitro calibration curves, the oxygen tension (pO₂,) was calculated from the measured R₁. Oxygen tension maps were then murine liver and spleen were produced (in 2.5 min) to demonstrate the technique and changes in tissue oxygenation as a function of breathing gas (air and carbogen (95% O₂ - 5% CO₂)) are presented. Tissue pO₂ maps from RIF-1 tumors (n = 5) were obtained in less than 10 min and changes in tumor pO₂ were studied when the breathing gals was switched from air to carbogen. The results from tumor pO₂ maps were compared with ¹⁹F MR spectroscopy measurements to check for consistency. Histogram analysis yielded an average liver and spleen pO₂ of 43 torr and 26 torr for RIF-1 tumors when the animals were breathing air. Statistically significant changes in tumor oxygenation as a function of breathing gas were obtained from both pO₂ maps (6 ± 2 torr, P < 0.05) and ¹⁹F MR spectroscopy (13 ± 3 torr, P < 0.01) as evaluated using the Student's paired t test.     

Oxygen-enhanced magnetic resonance ventilation imaging of the human lung at 0.2 and 1.5 T.

Lung ventilation imaging using inhaled oxygen as a contrast medium was performed using both a 0.2 and a 1.5 T clinical magnetic resonance (MR) scanner in eight volunteers. Signal-to-noise-ratios (SNRs) of the ventilation images as well as T1 values of the lung acquired with inhalation of 100% oxygen and room air were calculated. The SNR was 9.7 +/- 3.0 on the 0.2 T MR system and 69.5 +/- 28.8 on the 1.5 T system (P < 0.001). The mean T1 value on the 0.2 T MR system with subjects breathing room air was 632 +/- 54 msec; with 100% oxygen, it was 586 +/- 41 msec (P < 0.01). At 1.5 T, the mean values were 904 +/- 99 msec and 790 +/- 114 msec, respectively (P < 0.0001). We conclude that MR oxygen-enhanced ventilation imaging of the lung is feasible with an open configured 0.2 T MR system.     

Gas exchange parameters in radiotherapy patients during breathing of 2%, 3.5% and 5% carbogen gas mixtures

The gas mixture carbogen may be breathed by patients to enhance the oxygenation level and therefore the radiosensitivity of tumours. However, owing to the high CO2 content, its inhalation is associated with patient intolerance. Our aim was to determine a suitable carbon dioxide and oxygen gas mixture with similar enhancement of arterial oxygenation to 5% carbogen and with improved patient tolerance. 14 patients entered the study; of those 14, 8 were able to tolerate 2%, 3.5% and 5% carbogen mixtures as well as a control gas for sufficient time to allow successful arterial blood gas sampling. Gas exchange parameters were measured using a carbon dioxide monitor and a blood gas analyser. Arterial carbon dioxide tension ranged from 2.9 kPa to 6.82 kPa whilst breathing the carbogen mixtures, and arterial oxygen tension increased at least three-fold from basal values. There were no significant changes in the respiratory rate, heart rate and blood pH. The results suggest that 2% CO2 in O2 enhances arterial oxygen levels to a similar extent as 3.5% and 5% CO2 and that it is well tolerated.     

3T MR DW和BOLD对移植肾初步研究

目的:研究3.0T MR对移植肾DWI和BOLD成像的可行性.初步设定在3.0T MR上正常自体肾和正常移植肾的ADC值和R2*值范围.对比慢性移植肾病的ADC和R2*值,希望能无创性地加以鉴别.方法:对16例正常人及16例肾移植患者(8例为正常移植肾,8例慢性移植肾病)进行DWI和BOLD功能成像,在工作站上分别进行皮质和髓质ROI的定位,并记录ADC值和R2*值,对所得的结果进行统计学分析.结果:在3.0T MR上肾脏DWI和BOLD图像信噪比良好,能满足成像要求.自体肾和正常移植肾的皮髓质ADC值和R2*值的基线和变化范围均较以前报道的在1.5T上获得的高.慢性移植肾病的皮质ADC值、髓质R2*值及髓皮质R2*比值均较正常移植肾降低,并且有统计学意义.结论:3.0T MR扫描仪对肾脏DWI和BOLD功能成像是可行的,并且有利于对肾脏的功能研究,对慢性移植肾病的鉴别有一定帮助.     

Investigation of alternating and continuous experimental task designs during single finger opposition fMRI: a comparative study

The purpose of this study was to empirically investigate and compare the effects of alternating and continuous experimental task designs on blood oxygenation level dependent (BOLD) signal contrast. Six healthy volunteers underwent single-finger opposition functional magnetic resonance imaging (fMRI) using T2*-weighted echo planar imaging technique on a 1.5 T MR scanner. Two different acquisition patterns were tested: alternating (ABABAB) and continuous (AAABBB), rest: A, activation: B. The BOLD signal contrast within a primary motor cortex region of interest (ROI) was evaluated using normalized t-values (z-scores) and mean region of interest (ROI) intensity for the two patterns. Analysis of variance (ANOVA) on ROI mean z-score and signal intensities demonstrate that the alternating pattern of administering rest and activation epochs produced a more robust statistical difference than a continuous pattern. The results showed that different patterns of acquisition yield differences in the BOLD signal at field strength of 1.5 T, and that an alternating task design can be considered more optimal than a continuous task design.     

Morphological and carbogen-based functional MRI of a chemically induced liver tumor model in mice.

A multifocal mouse liver tumor model chemically induced with 5,9-dimethyl-7H-dibenzo[c,g]carbazole was investigated by respiratory-triggered morphological and functional MRI (fMRI) at 4.7 Tesla. The model is characterized by the presence of two tumor types: hypovascular cholangioma and vascularized hepatocellular carcinoma (HCC). Growth curves measured by 3D-MRI showed limited growth of cholangiomas and rapid growth of HCCs after a latency of about 25 weeks. Functional imaging based on T(2) (*)-weighted fast gradient-echo MRI and carbogen breathing was optimized for liver imaging in mice. A response to carbogen was observed in HCCs but not in cholangiomas. Transversal analysis (50 HCCs) of signal change upon carbogen revealed four different types of response patterns: 1) signal increase upon carbogen administration (74%); 2) small or insignificant signal change (10%), 3) transient signal decrease and delayed increase (8%), and 4) signal decrease (8%). Longitudinal follow-up of a subgroup (N = 17) showed that an initially observed type 1 response, attesting to the presence of a functional vasculature, remained stable for at least 3 weeks in 14 HCCs. A switch from a type 1 response to another response type may be useful for demonstrating, in a noninvasive manner, a disturbance of tumor vasculature induced by anti-vascular or anti-angiogenic therapy.     

Spatial and temporal characteristics of physiological noise in fMRI at 3T

RATIONALE AND OBJECTIVES: Physiological noise in blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) has been shown to have characteristics similar to the BOLD signal itself, suggesting that it may have a vascular dependence. In this study, we evaluated the influence of physiological noise in fMRI as revealed by the differences in vasculature sensitivity of gradient-echo echo-planar imaging (GE-EPI) and spin-echo EPI (SE-EPI). MATERIALS AND METHODS: The contribution of physiological noise to the fMRI signal during activation of the visual cortex was assessed by comparing its temporal characteristics with respect to echo time (TE), using both GE-EPI and SE-EPI. The correlation of the noise in fMRI with apparent diffusion coefficient (ADC) and the number of components required to describe its variance, as determined by principal-component analysis (PCA), were also assessed. RESULTS: The SE-EPI data were less affected by a TE-dependence of noise, in contrast to the apparent physiological noise in GE-EPI. Voxel-wise analysis revealed that total apparent noise increased as ADC values increased, and the relationship was different for GE-EPI and SE-EPI. PCA revealed that while the number of components characterizing the noise in SE-EPI data increased in a TE-dependent manner, approaching that of white noise at long echo time, the number of components from GE-EPI data was TE-independent. CONCLUSIONS: The difference in sensitivities to physiological noise between SE-EPI and GE-EPI suggests that extravascular BOLD processes around draining veins contribute significantly to physiological noise in BOLD fMRI, and the suppression of this noise component may enhance SE-EPI BOLD sensitivity at higher fields.     

Systematic investigation of balanced steady-state free precession for functional MRI in the human visual cortex at 3 Tesla.

Previous studies have applied balanced steady-state free precession (bSSFP) to functional brain imaging. Methods that exploit the strong frequency dependence of the MR signal in the bSSFP transition band are strongly affected by field inhomogeneity and frequency drifts. Recent bSSFP studies using "on-resonance" (in the bSSFP passband) acquisition claimed that higher sensitivity was achieved compared to traditional fMRI methods. However, the contrast mechanism that generates activation-related signal changes in bSSFP imaging is not yet fully understood. We performed a systematic study of on-resonance bSSFP signal behavior using a multiecho balanced SSFP sequence with different TRs at 3 Tesla. We conclude that intravoxel dephasing, or the off-resonance averaged steady state, dominates the bSSFP signal decay and determines the bSSFP fMRI contrast. Experimental findings were confirmed by simulations based on existing theories for signal formation around blood vessels in inhomogeneous tissues. The activation-induced signal change in on-resonance bSSFP increases with TE, and the TE dependence of the contrast-to-noise ratio (CNR) in bSSFP is similar to that in gradient echo-planar imaging (GE-EPI). However, GE-EPI has a significantly higher CNR efficiency.     

Whole tumour perfusion of peripheral lung carcinoma: evaluation with first-pass CT perfusion imaging at 64-detector row CT

AIM: To prospectively assess the feasibility of a whole-tumour perfusion technique using 64-detector row computed tomography (CT) and to analyse the variation of CT perfusion parameters in different histological types, sizes, and metastases in patients with peripheral lung carcinoma. METHODS AND MATERIALS: Ninety-seven pathologically proved peripheral lung carcinomas (less than 5 cm in largest diameter) underwent dynamic contrast-enhanced CT using a 64-detector row CT machine. Small amounts of iodinated contrast medium with a sharp bolus profile (50 ml, 6-7 ml/s), and 12 repeated fast acquisitions encompassing the entire tumour lesion were adopted to quantify perfusion of the whole-tumour during first-pass of contrast medium. Four kinetic parameters, including perfusion, peak enhancement intensity (PEI), time to peak (TTP), and blood volume (BV), were measured and statistically compared among different histological types, sizes, and metastases. RESULTS: Mean values for perfusion, PEI, TTP, and BV of the 97 lung carcinomas were 57.5+/-45.4 ml/min/ml (range 5.9-243 ml/min/ml), 53.4+/-40.6 HU (range 10.3-234.4 HU), 34+/-11s (range 11-60s), and 30.1+/-21.7 ml/100g (range 3.9-113.4 ml/100g), respectively. No statistical differences were found between the histological types regarding the perfusion parameters (p>0.05). Perfusion, PEI, and BV of stage T2 tumours were significantly lower than those of stage T1 tumours (all p < 0.05), whereas no statistically significant differences was found between other stages of tumours (all p>0.05). Perfusion of the tumours with distant metastasis was significantly higher than that of the tumours without distant metastasis (p<0.05), but there was no statistically significant difference between nodal metastasis positive and negative groups (p>0.05). CONCLUSION: The present study of first-pass perfusion imaging using 64-detector row CT could provide a feasible method for assessment of whole-tumour perfusion. CT perfusion parameters of peripheral lung carcinoma may be associated with tumour size and distant metastasis.     

High-resolution magnetic resonance of the extracranial facial nerve and parotid duct: demonstration of the branches of the intraparotid facial nerve and its relation to parotid tumours by MRI with a surface coil

AIM: To investigate the usefulness of high-resolution MR imaging in the evaluation of the extracranial facial nerve, compared with surgical findings. MATERIALS AND METHODS: Thirteen patients with benign parotid tumours were studied on a 1.5-T MR system with a 3 in circular surface coil. High-resolution T1-weighted spin-echo, T2-weighted fast spin-echo, and three-dimensional gradient-recalled acquisition in the steady state (GRASS) images were obtained in the axial planes. Oblique reformatted images were generated. Tumours, parotid ducts and facial nerves were identified on these images. The relationship of the tumours to the facial nerves was confirmed at surgery. RESULTS: Facial nerves appeared as linear structures of low intensity on all pulse sequences. The main trunks and cervicofacial and temporofacial divisions of the facial nerves were identified in 100%, 84.1% and 53.8% of GRASS images, respectively. Parotid ducts appeared as structures of low intensity on T1-weighted (66.6%) and GRASS images (81.8%), and as structures of very high intensity on T2-weighted images (91.7%). The relationships of the tumours to the facial nerves were correctly diagnosed in 11 (91.7%) of 12 cases. CONCLUSION: High-resolution MR imaging depicts the extracranial facial nerve and the parotid duct, and is useful for preoperative evaluation of parotid gland tumours.     

Application of an exogenous hyperoxic contrast agent in MR mammography: initial results

There is interest in applying novel methods to dynamic MR mammography (MRM). One such possibility is to administer an exogenous hyperoxic contrast agent, such as carbogen (95–98% O₂ and 2–5% CO₂) or pure oxygen (100% O₂). We report our first experiences with these agents in a patient with an invasive lobular carcinoma. Fourteen dynamic series were acquired with an rf-spoiled 2D multislice gradient echo sequence, including three measurements while breathing air, four measurements with 100% oxygen, three measurements with air and four measurements with carbogen. Afterwards, 0.1 mmol/kg bw of Gd-DTPA was administered to obtain dynamic T1-weighted double-echo 3D axial gradient echo images (TR/TE₁/TE₂/=7.8 ms/2 ms/4.76 ms/15°) every 90 s up to 4.5 min after injection. The lesion was well delineated on the contrast-enhanced images, contrary to magnitude images reconstructed from the raw data sets acquired during air/oxygen/carbogen breathing. A ROI-based median-filtered signal-time course revealed a tumor signal increase of roughly 15% between scans acquired during air and oxygen breathing. Though preliminary, these first results are encouraging concerning the exploration of these alternative contrast agents in MRM in greater detail.     

Tumor vascular architecture and function evaluated by non-invasive susceptibility MRI methods and immunohistochemistry

PURPOSE: To investigate the physiological origins responsible for the varying blood oxygenation level dependent (BOLD) magnetic resonance imaging (MRI) responses to carbogen (95% O(2)/5% CO(2)) breathing observed with different tumor types. MATERIALS AND METHODS: Susceptibility contrast-enhanced MRI using the exogenous blood pool contrast agent NC100150 to determine blood volume and vessel size, and immunohistochemical-derived morphometric parameters, were determined in GH3 prolactinomas and RIF-1 fibrosarcomas, both grown in mice, which exhibited very different BOLD responses to carbogen. RESULTS: Administration of NC100150 increased the R(2)* and R(2) rates of both tumor types, and indicated a significant four-fold larger blood volume in the GH3 tumor. The ratio deltaR(2)*/deltaR(2) showed that the capillaries in the GH3 were two-fold larger than those in the RIF-1, in agreement with morphometric analysis. Carbogen breathing induced a significant 25% decrease in R(2)* in the GH3 prolactinoma, whereas the response in the RIF-1 fibrosarcoma was negligible. CONCLUSION: Low blood volume and small vessel size (and hence reduced hematocrit) are two reasons for the lack of R(2)* change in the RIF-1 with carbogen breathing. BOLD MRI is sensitive to erythrocyte-perfused vessels, whereas exogenous contrast agents interrogate the total perfused vascular volume. BOLD MRI, coupled with a carbogen challenge, provides information on functional, hemodynamic tumor vasculature.