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.     

Organ-specific effects of oxygen and carbogen gas inhalation on tissue longitudinal relaxation times.

Molecular oxygen has been previously shown to shorten longitudinal relaxation time (T1) in the spleen and renal cortex, but not in the liver or fat. In this study, the magnitude and temporal evolution of this effect were investigated. Medical air, oxygen, and carbogen (95% oxygen/5% CO2) were administered sequentially in 16 healthy volunteers. T1 maps were acquired using spoiled gradient echo sequences (TR=3.5 ms, TE=0.9 ms, alpha=2 degrees/8 degrees/17 degrees) with six acquisitions on air, 12 on oxygen, 12 on carbogen, and six to 12 back on air. Mean T1 values and change in relaxation rate were compared between each phase of gas inhalation in the liver, spleen, skeletal muscle, renal cortex, and fat by one-way analysis of variance. Oxygen-induced T1-shortening occurred in the liver in fasted subjects (P<0.001) but not in non-fasted subjects (P=0.244). T1-shortening in spleen and renal cortex (both P<0.001) were greater than previously reported. Carbogen induced conflicting responses in different organs, suggesting a complex relationship with organ vasculature. Shortening of tissue T1 by oxygen is more pronounced and more complex than previously recognized. The effect may be useful as a biomarker of arterial flow and oxygen delivery to vascular beds.     

Blood oxygenation level-dependent (BOLD) MRI of human skeletal muscle at 1.5 and 3 T

Purpose:

To evaluate the dependence of skeletal muscle blood oxygenation level‐dependent (BOLD) effect and time course characteristics on magnetic field strength in healthy volunteers using an ischemia/reactive hyperemia paradigm.

Materials and Methods:

Two consecutive skeletal muscle BOLD magnetic resonance imaging (MRI) measurements in eight healthy volunteers were performed on 1.5 T and 3.0 T whole‐body MRI scanners. For both measurements a fat‐saturated multi‐shot multiecho gradient‐echo EPI sequence was applied. Temporary vascular occlusion was induced by suprasystolic cuff compression of the thigh. T2* time courses were obtained from two different calf muscles and characterized by typical curve parameters. Ischemia‐ and hyperemia‐induced changes in R2* (ΔR2*) were calculated for both muscles in each volunteer at the two field strengths.

Results:

Skeletal muscle BOLD changes are dependent on magnetic field strength as the ratio ΔR2*(3.0 T)/ΔR2*(1.5 T) was found to range between 1.6 and 2.2. Regarding time course characteristics, significantly higher relative T2* changes were found in both muscles at 3.0 T.

Conclusion:

The present study shows an approximately linear field strength dependence of ΔR2* in the skeletal muscle in response to ischemia and reactive hyperemia. Using higher magnetic fields is advisable for future BOLD imaging studies of peripheral limb pathologies. J. Magn. Reson. Imaging 2012;35:1227‐1232. © 2012 Wiley Periodicals, Inc.     

胚胎发育不良性神经上皮瘤的MRI表现特征

目的 探讨胚胎发育不良性神经上皮瘤（DNT）的MRI表现特征。方法 对经手术病理证实的6例DNT的MRI材料进行回顾性分析，总结DNT的MRI表现特征。结果 6例患者的肿瘤均局限于皮层或以皮层为主，呈三角形假囊肿样，T1WI呈低信号，T2WI呈高信号；T2水抑制像上边缘和分隔呈高信号，其他部分呈等偏低信号；扩散加权像（DWI）上呈低或等偏低信号，表观扩散系数（ADC）图呈ADC值升高；MR波谱测定肿瘤胆碱（Cho）峰和肌酸（Cr）峰改变不明显，N-乙酰天门冬氨酸（NAA）较正常参照侧降低，但降低不明显；增强无强化；瘤体夹杂细条索状等信号分隔；无瘤周水肿，无占位效应；肿瘤邻近的颅骨内板发育不良。结论 胚胎发育不良性神经上皮瘤MRI表现较具特征性，有助于术前正确诊断。     

直肠绒毛状肿瘤的MRI诊断

目的 探讨直肠绒毛状肿瘤MRI表现,以提高对该肿瘤的诊断水平.方法 回顾性分析本院经病理证实的15例直肠绒毛状肿瘤(绒毛管状腺瘤9例,绒毛状腺瘤6例)的MRI资料.结果 15例绒毛状肿瘤中7例表现为绒球状,可见厚柄,5例表现为结节状,3表现为乳头状;15例T1WI均表现为低信号,T.WI为稍低信号;DWI序列9例表现为中央低信号,周围呈高信号,余6例表现均匀稍高信号;动态增强扫描7例表现为病灶中央枯树枝样强化,5例呈均匀轻中度强化,3表现为脑回状强化;11例合并不同程度不典型增生,4例合并癌变,其直径均＞3 cm,其中2例表现为绒球状、中央呈枯树枝样强化,2例表现为乳头状,呈脑回状强化.结论 绒毛状肿瘤MRI表现形式多样,直肠MRI扫描能够显示直肠绒毛状肿瘤的典型表现及合并癌变的MRI表现.     

BOLD contrast fMRI of whole rodent tumour during air or carbogen breathing using echo-planar imaging at 1.5 T

The aim of this study was to evaluate the feasibility of functional MR imaging (fMRI) at 1.5 T, exploiting blood oxygenation level-dependent (BOLD) contrast, for detecting changes in whole-tumour oxygenation induced by carbogen (5% CO2+95% O2) inhalation of the host. Adult WAG/Rij rats with rhabdomyosarcomas growing subcutaneously in the lower flank were imaged when tumours reached sizes between 1 and 11 cm3 (n=12). Air and carbogen were alternatively supplied at 2 l/min using a snout mask. Imaging was done on a 1.5-T MR scanner using a T2*-weighted gradient-echo, echo-planar imaging (GE-EPI) sequence. Analysis of the whole-tumour EPI images was based on statistical parametric maps. Voxels with and without signal intensity changes (SIC) were recorded. Significance thresholds were set at p<0.05, corrected for multiple comparisons. In continuous air breathing condition, 3 of 12 tumours showed significant negative SIC and 1 tumour had a clear-cut positive SIC. The remaining tumours showed very little or no change. When switching to carbogen breathing, the SIC were significantly positive in 10 of 12 tumours. Negative SIC were present in 4 tumours, of which three were simultaneously characterised by positive SIC. The overall analysis indicated that 6 of the 12 tumours could be considered as strong positive responders to carbogen. Our research demonstrates the applicability of fMRI GE-EPI at 1.5 T to study whole-tumour oxygenation non-invasively. The observed negative SIC during air condition may reflect the presence of transient hypoxia during these measurements. Selection of tumours on the basis of their individual response to carbogen is possible, indicating a role of such non-invasive measurements for using tailor-made treatments.     

子宫恶性苗勒氏管混合瘤的 MR诊断

目的：探讨子宫恶性苗勒氏管混合瘤（MMMT）的MR表现特点，提高对其认识。方法回顾性分析6例MMMT患者的临床资料及MR表现特征，所有病例均经手术病理证实。结果多数肿瘤体积较大，宫腔内肿瘤以膨胀性生长为主，伴局部肌层浸润。MR表现为信号混杂的囊实性肿块，可合并出血，肿瘤不均匀强化，较为典型的“蜂窝状”结构为其较为特征的MR征象。结论 MMMT有较为特征的MR影像表现，MR对其有较高的诊断价值。     

前列腺疾病吸入5%二氧化碳混合气体BOLD-MRI与微血管特征的对照研究

目的：探讨吸入5%二氧化碳混合气体BOLD-MRI与前列腺增生(BPH)和前列腺癌(PCa)中微血管特征的对应关系。方法采用美国 GE Signa Excite HD 3.0T超导型磁共振成像仪和腹部相控阵线圈,在吸入5%二氧化碳混合气体行 BOLD-MRI。画取正常前列腺外周带(PZ)、中央腺区(CZ)、BPH 和PCa感兴趣区(ROI),记录时间-信号强度曲线(TIC)和信号强度平均增加率。免疫组化分析BPH 和PCa微血管形态学特征：平均直径、平均面积、平均周长及异型指数。结果 CZ、PZ、BPH 及 PCa 区信号强度于吸入混合气体后高于吸入混合气体前(P<0.05);吸入混合气体后正常 CZ、PZ、BPH 及 PCa 区的相对平均信号强度增加率分别为(5.07±1.08)%、(2.78±1.13)%、(6.44±2.02)%和(1.77±0.40)%,BPH 和PCa组织中的 MVD数分别为12.32±3.14和30.22±11.19(P<0.01);PCa血管的平均直径、平均面积、平均周长及异型指数均小于 BPH 的相应指标(P<0.01)。结论前列腺疾病吸入混合气体BOLD-MRI表现与组织的微血管特征有关,有助于评价组织微血管结构功能状态。     

Modified oxygen mask to induce target levels of hyperoxia and hypercarbia during radiotherapy: A more effective alternative to carbogen

Purpose: Carbogen has long been under investigation as an adjuvant to radiotherapy of tumors. A major factor confounding its evaluation is its inconsistency in raising blood partial pressure of CO₂ (pCO₂). We investigated whether a new partial rebreathing method would provide better control of pCO₂ than carbogen.

Methods and materials: We compared the efficacy of each method in 10 healthy volunteers. Volunteers breathed 1.5, 3 and 5% carbogen in 5-min stages via the usual non-rebreathing circuit. All the volunteers then breathed 100% O₂ through a commercial sequential gas delivery (SGD) circuit modified by attaching a reservoir to its exhalation port. Hypercarbia was induced by step reductions in oxygen flow to the SGD circuit. We monitored minute ventilation and end-tidal pCO₂ (ETpCO₂) as a surrogate for its arterial value.

Results: Inhalation of 1.5 and 3% carbogen did not increase ETpCO₂ from baseline (40 ± 1.5 mmHg); 5% carbogen increased ETpCO₂ to 45 ± 1.6 mmHg (p < 0.001). With the SGD circuit, reducing O₂ flow to 4.3 ± 0.7 l/min increased ETpCO₂ in all subjects from 41 ± 2.0 mmHg (baseline) to 46 ± 2.1 mmHg (p < 0.001). Voluntary hyperventilation reduced ETpCO₂ with 5% carbogen but not with SGD (p = 0.379).

Conclusions: We confirm previous observations that carbogen inhalation does not result in a predictable rise in ETpCO₂ and suggest that a precise and stable target ETpCO₂ can instead be induced by simply controlling O₂ flow into a modified SGD circuit. We hoped that the reliable control of pCO₂ will enable studies that address first, the efficacy of raising ETpCO₂ on specific tumor blood flow, and eventually, its benefit as an adjuvant to radiotherapy.     

BOLD MRI对早期糖尿病肾病大鼠肾实质缺氧的实验研究

目的采用3.0T超导型磁共振对早期糖尿病肾病(DN)大鼠进行BOLD成像研究,探讨DN大鼠肾脏皮质及髓质R2*值变化情况。方法20只SD雄性大鼠随机分为正常对照组(NC组)10只及糖尿病肾病组(DN组)10只,腹腔注射链脲佐菌素建立DN模型。3周后予以进行MRI扫描,扫描完成后立即处死大鼠,对每只大鼠的双肾组织取样进行病理检查。所有MRI图像传输到GE后处理工作站,由2名高年资医师盲法读片及测量每只大鼠双肾皮质和髓质R2*值。最后进行统计学分析。结果NC组大鼠皮质与髓质R2*值之间无显著统计学意义,而DN组大鼠有;DN组大鼠无论皮质及髓质,其R2*值均高于NC组,差异均有显著统计学意义。结论BOLD MRI对早期DN大鼠肾脏氧合水平无创性评估具有可行性,对临床早期治疗DN有望提供帮助。     

低氧致脑水肿的磁共振扩散加权成像和病理观察

目的 通过对模拟高原低氧致脑水肿的磁共振扩散加权成像和病理改变的研究,探讨高原脑水肿的病理基础.方法 选320～380 g的雄性Wistar大鼠32只,按体重随机分为常氧组、4 000 m组、6 000 m组和8 000 m组各8只.后3组动物置于低压舱中模拟海拔4 000 m、6 000 m、8 000 m高原低氧环境持续8 h后,对所有大鼠进行扩散加权成像检查及脑组织的光镜和电镜观察.结果 低氧处理的各组扩散加权成像均出现低强度信号,表观扩散常数值升高.与常氧组比较,4 000 m组表观扩散常数值的升高无明显差异,6 000 m组和8 000 m组表观扩散常数值升高有显著性差异.病理检查显示,4 000 m组脑组织呈现混合性脑水肿,血脑屏障轻度损伤;6 000 m组以血管源性脑水肿为主,血脑屏障损伤加重;8 000 m组重度血管源性脑水肿,血脑屏障破坏解体.结论 低氧所致的脑水肿主要是血管源性脑水肿,其病理基础是低氧导致的血脑屏障损害.     

附睾腺瘤样瘤 MRI 表现

目的：探讨附睾腺瘤样瘤(AT)MRI 的影像表现及诊断价值。方法回顾性分析5例经组织病理证实的附睾 AT 患者的 MRI 表现,并复习国内外文献。结果4例附睾肿块 T1 WI 和 T2 WI 呈与睾丸类似的中等信号,增强扫描肿块呈中等强化,边缘呈稍高强化；1例合并继发性梗死及慢性肉芽肿炎,T1 WI 呈中等不均信号,T2 WI 呈略低信号,DWI 呈高信号,动态增强呈环形明显强化；5例均见少量鞘膜积液。结论AT 是附睾罕见良性肿瘤,MRI 表现有一定的特征性,有助于术前诊断。     

高场MRI对胃肠间质瘤的诊断

目的 分析高场MRI对胃肠间质瘤(GIST)影像表现,探讨其对该肿瘤的诊断价值.方法 对经病理证实的45例GIST的高场磁共振影像学资料进行回顾分析.结果 45例GIST中,发生于骶前2例,会阴部5例,小肠5例,直肠10例,胃内23例.其中有11例为术后复发,余34例为新发.高场MRI表现为不均匀的肿块信号影,体积小者信号均匀,体积大者信号不均匀,可出现囊变、坏死、出血等;增强后肿块实性部分异常强化信号影,坏死、囊变区无明显强化信号影.肿瘤边界清晰或不清晰,邻近组织受压,易发生转移或腹腔内种植.病理结果显示: 肿瘤大体,切面呈灰白、灰红色,可见包膜.镜下主要由形态多样、数量不等的梭形细胞构成.免疫组化CD34(+)为43例;CD117(+)为40例;Desmin(+)为18例;Vimentin(+)为15例.结论 高场MRI对GIST可以准确定位,对其诊断及鉴别诊断具有重要价值.     

Spectroscopic imaging of the water resonance with short repetition time to study tumor response to hyperoxia

A variety of treatments that modulate tumor oxygen tension are used clinically to improve the outcome of radiotherapy. High resolution, noninvasive measurements of the effects of these treatments would greatly facilitate the development of improved therapies and could guide treatment of cancer patients. Previous work demonstrated that magnetic resonance (MR) gradient echo imaging of the water proton resonance detects changes in T₂* and T₁ in tumors during hyperoxia that may reflect increased tumor oxygenation. This report describes the use of high resolution MR spectroscopic imaging with short repetition time (TR = 0.2 s) to improve the accuracy with which changes in T₂* and T₁ are measured. Mammary adenocarcinomas grown in the hind limbs of rats were studied. Carbogen inhalation was used to induce hyperoxia. A single 2-mm slice through the center of tumors and underlying muscle was imaged at 4.7 Tesla with in-plane resolution of approximately 1.2 mm and frequency resolution of 5.8 Hz. The peak integral increased by an average of 6% in tumors during carbogen inhalation suggesting a decrease in T₁ (n = 8, P <0.001). Peak height increased by an average of 15% in tumors during carbogen inhalation (n = 8, P <0.001). The large difference between increases in peak height and peak integral demonstrates that the width of the water resonance decreased. Assuming a Lorentzian lineshape, an average increase of 12% in T₂* was observed in tumors. In muscle, peak integral and peak height increased slightly (about 1.2% and 3%. respectively; P <0.02) during carbogen inhalation but no significant change in T₂*was observed. Spectroscopic imaging detects changes in the water proton resonance in tumors during hyperoxia accurately and reproducibly with high signal-to-noise ratio and allows clear separation of T₁ and T₂* effects. Increases in T₂* may be due to decreased deoxyhemoglobin in tumor blood vessels (i.e., the BOLD effect) and may provide a clinically useful index of increases in tumor oxygenation.     

Contrast/Noise ratio on conventional MRI and choline/creatine ratio on proton MRI spectroscopy accurately discriminate low-grade from high-grade cerebral gliomas

RATIONALE AND OBJECTIVES: Histopathology is the gold standard to establish the grade of brain tumors but biopsy and/or surgery are not always possible. The aim of this study is to determine whether histological grade of tumors may be predicted by means of conventional gadolinium-enhanced MRI and proton magnetic resonance spectroscopy (MRS). MATERIALS AND METHODS: In this study, we included 35 consecutive patients with single brain tumors and final histopathological verification: 12 had low-grade glioma, 16 had high-grade glioma, and 7 had single metastasis. Initially, we carried out T1 and T2 MRI paying attention to the following features: border definition, mass effect, heterogeneity of signal, perilesional edeme, hemorrhage, necrosis, and corpus callosum invasion. Gadolinium-enhancement was evaluated with the contrast-to-noise ratio (CNR). Next, single-voxel proton MRS was carried out to measure the absolute values of metabolites (N-acetyl-aspartate, creatine, choline, and myo-inositol) and their ratios in the area of maximum contrast enhancement. RESULTS: We found that gadolinium-enhancement measured with the CNR (CNR > 35.86) predicted malignancy at 82.6% sensitivity and 91.7% specificity (area under the curve, 0.88; 95% confidence interval [CI], 0.73-0.97). With regard to MRS a choline/creatine ratio higher than 1.56 predicted malignancy at 88.9% sensitivity and 91.7% specificity (area under the curve, 0.94; 95% CI, 0.78-0.99). When we combined the CNR value, the choline/creatine ratio, and the presence of lactates in a model of discriminant analysis the predictive power improved significantly with an area under the curve of 0.99% (95% CI, 0.87-1). However, the used techniques were unable to distinguish metastases from high-grade gliomas accurately. CONCLUSIONS: The intensity of contrast enhancement measured with the CNR, the choline/creatine ratio, and the presence of lactate were the most powerful variables to predict malignancy in brain tumors. The CNR is a simple, objective, and useful tool in the initial assessment of gliomas and metastases.     

磁共振成像在常见脑肿瘤边缘研究中的进展

综述磁共振成像技术,包括弥散加权成像（包括弥散张量成像）、磁共振氢质子波谱分析及血氧水平依赖的皮层激发功能定位成像在星形细胞瘤、转移瘤、脑膜瘤边缘研究中的应用。     

胰腺导管内乳头状粘液样瘤的MRI诊断分析

目的:探讨胰腺导管内乳头状粘液样瘤的MRI诊断价值。方法:回顾分析经手术病理证实的9例胰腺导管内乳头状粘液样瘤的MRI表现,其中腺瘤3例、交界性腺瘤3例、腺癌1例。结果:①主胰管型3例,MRI表现为主胰管弥漫性或节段性扩张,十二指肠乳头肿大;②支胰管型5例,表现为胰腺囊性病灶多位于胰头钩突部,呈单囊或多囊状,可见分隔、壁结节,和主胰管相通;③混合型1例,该型包括与主胰管相连囊性病灶、主胰管扩张。结论:胰腺导管内乳头状粘液样瘤的影像表现有一定特征性,MRI对其诊断有重要价值。     

Transient decrease in tumor oxygenation after intravenous administration of pyruvate

MRI using hyperpolarized (13) C-labeled pyruvate is a promising tool to biochemically profile tumors and monitor their response to therapy. This technique requires injection of pyruvate into tumor-bearing animals. Pyruvate is an endogenous entity but the influence of exogenously injected bolus doses of pyruvate on tumor microenvironment is not well understood. In this study, the effect of injecting a bolus of pyruvate on tumor oxygen status was investigated. EPR oxygen imaging revealed that the partial pressure of oxygen (pO(2)) in squamous cell carcinoma implanted in mice decreased significantly 30 min after [1-(13) C]pyruvate injection, but recovered to preinjection levels after 5 h. Dynamic contrast-enhanced-MRI studies showed that, at the dose of pyruvate used, no changes in tumor perfusion were noticed. Immunohistochemical analysis of hypoxic marker pimonidazole independently verified that the squamous cell carcinoma tumor transiently became more hypoxic by pyruvate injection. Efficacy of radiotherapy was suppressed when X-irradiation was delivered during the period of pyruvate-induced transient hypoxia. These results suggest importance of taking into account the transient decrease in tumor pO(2) after pyruvate injection in hyperpolarized (13) C MRI, because tumor oxygen status is an important factor in determining outcomes of therapies.