Single, slice-specific z-shim gradient pulses improve T2*-weighted imaging of the spinal cord

T2*-weighted imaging of the spinal cord suffers from signal dropouts that hamper blood-oxygenation-level-dependent functional magnetic resonance imaging (fMRI). They are due to field inhomogeneities caused by the different magnetic susceptibilities of the vertebrae and the intervertebral disks that vary periodically along the cord and, thus, cannot be compensated appropriately with conventional (constant) shimming. In this study, a single, slice-specific gradient pulse (“z-shim”) is applied in echo-planar imaging of axial sections in order to compensate for the corresponding through-slice signal dephasing without affecting the acquisition time, i.e. the temporal resolution. Based on a reference acquisition sampling a range of compensation moments, the value yielding the maximum signal amplitude within the spinal cord is determined for each slice. Severe N/2 ghosting for larger compensation moments is avoided by applying the gradient pulse after the corresponding reference echoes. Furthermore, first-order flow compensation in the slice direction of both the slice-selection and the z-shim gradient pulse considerably reduces signal fluctuations in the cerebro-spinal fluid surrounding the spinal cord, i.e. would minimize ringing artifacts in fMRI. Phantom and in vivo experiments show the necessity to use slice-specific compensation moments in the presence of local susceptibility differences. Measurements performed in a group of 24 healthy volunteers at 3T demonstrate that this approach improves T2*-weighted imaging of axial sections of the cervical spinal cord by (i) increasing the signal intensity (overall by about 20%) and (ii) reducing signal intensity variations along the cord (by about 80%). Thus, it may help to improve the feasibility and reliability of fMRI of the spinal cord.     

Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9

Dysfunction of the nigrostriatal system is the major cause of Parkinson's disease (PD). This brain region is therefore an important target for gene delivery aiming at disease modeling and gene therapy. Recombinant adeno-associated viral (rAAV) vectors have been developed as efficient vehicles for gene transfer into the central nervous system. Recently, several serotypes have been described, with varying tropism for brain transduction. In light of the further development of a viral vector-mediated rat model for PD, we performed a comprehensive comparison of the transduction and tropism for dopaminergic neurons (DNs) in the adult Wistar rat substantia nigra (SN) of seven rAAV vector serotypes (rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9). All vectors were normalized by titer and volume, and stereotactically injected into the SN. Gene expression was assessed non-invasively and quantitatively in vivo by bioluminescence imaging at 2 and 5 weeks after injection, and was found to be stable over time. Immunohistochemistry at 6 weeks following injection revealed the most widespread enhanced green fluorescence protein expression and the highest number of positive nigral cells using rAAV 2/7, 2/9 and 2/1. The area transduced by rAAV 2/8 was smaller, but nevertheless almost equal numbers of nigral cells were targeted. Detailed confocal analysis revealed that serotype 2/7, 2/9, 2/1 and 2/8 transduced at least 70% of the DNs. In conclusion, these results show that various rAAV serotypes efficiently transduce nigral DNs, but significant differences in transgene expression pattern and level were observed.     

2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography uptake in a giant adrenal myelolipoma.

Incidental adrenal lesions found on anatomic imaging are not uncommon. 2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) imaging is highly accurate in the differentiation of benign from malignant adrenal lesions, both in patients with proven malignancy and with adrenal lesions detected incidentally. A 60-year-old white female with a history of lower mid-back pain underwent computerized tomography (CT) imaging that identified a 15-cm complex mass within the left adrenal gland with soft tissue, cystic, and adipose components. FDG-PET imaging showed significant hypermetabolic activity within portions of the mass with central photopenia suggesting a malignant lesion with central necrosis. Surgical excision and pathological examination, however, revealed a benign adrenal myelolipoma with extensive adenomatous and hematopoietic elements. Prior reports of adrenal myelolipoma evaluated with FDG-PET imaging have described no significant FDG uptake within these benign tumors. This case is an unusual example of histologically proven benign adrenal myelolipoma that was hypermetabolic on FDG-PET imaging. Correlation of pathologic and imaging findings demonstrated that the hypodense regions on CT were hypometabolic on FDG-PET and corresponded to cystic necrosis and adipose elements, whereas the adenomatous and hematopoietic elements were hypermetabolic.     

Proceedings of the 2011 World Molecular Imaging Congress,San Diego,CA, USA,September 7-10, 2011

The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; ) to students, researchers, and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, X-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1,000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4,250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration as well as a comma separated values file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, pre-clinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities, and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments, or suggestions for further improvement of the database by writing to the editors at micad@nlm.nih.gov.     

MR molecular imaging of HER‐2 in a murine tumor xenograft by SPIO labeling of anti‐HER‐2 affibody

In vivo molecular imaging is a rapidly growing research area both for basic and clinical science. Non‐invasive imaging of in vivo conditions at the molecular level increases understanding of the biological characteristics of normal and diseased tissues without the need for invasive surgical procedures. Among the various imaging modalities, magnetic resonance imaging (MRI) has garnered interest as a molecular imaging modality due to its high spatial resolution. Here, we have demonstrated that the combined use of HER‐2 targeting affibody, a small 7 kDa molecule that behaves similarly to antibodies, and superparamagnetic iron oxide (SPIO) can non‐invasively image HER‐2 expressing cells or tissues both in vitro and in vivo by MRI. This preliminary study demonstrates that affibody‐SPIO is a feasible, target‐specific contrast agent for in vivo MR molecular imaging. Copyright © 2010 John Wiley & Sons, Ltd.     

Performance characterization of low-cost,high-speed,portable pulsed laser diode photoacoustic tomography (PLD-PAT) system

Photoacoustic tomography systems that uses Q-switched Nd:YAG/OPO pulsed lasers are expensive, bulky, and hence limits its use in clinical applications. The low pulse repetition rate of these lasers makes it unsuitable for real-time imaging when used with single-element ultrasound detector. In this work, we present a pulsed laser diode photoacoustic tomography (PLD-PAT) system that integrates a compact PLD inside a single-detector circular scanning geometry. We compared its performance against the traditional Nd:YAG/OPO based PAT system in terms of imaging depth, resolution, imaging time etc. The PLD provides near-infrared pulses at ~803 nm wavelength with pulse energy ~1.4 mJ/pulse at 7 kHz repetition rate. The PLD-PAT system is capable of providing 2D image in scan time as small as 3 sec with a signal-to-noise ratio ~30. High-speed and deep-tissue imaging is demonstrated on phantoms and biological samples. The PLD-PAT system is inexpensive, portable, allows high-speed PAT imaging, and its performance is as good as traditional expensive OPO based PAT system. Therefore, it holds promises for future translational biomedical imaging applications.OCIS codes: (170.5120) Photoacoustic imaging, (170.3880) Medical and biological imaging, (170.0110) Imaging systems, (140.2010) Diode laser arrays     

Real-time spatial compound imaging: Application to breast, vascular, and musculoskeletal ultrasound

Real-time spatial compound imaging (SonoCT) is an ultrasound technique that uses electronic beam steering of a transducer array to rapidly acquire several (three to nine) overlapping scans of an object from different view angles. These single-angle scans are averaged to form a multiangle compound image that is updated in real time with each subsequent scan. Compound imaging shows improved image quality compared with conventional ultrasound, primarily because of reduction of speckle, clutter, and other acoustic artifacts. Early clinical experience suggests that real-time spatial compound imaging can provide improved contrast resolution and tissue differentiation that is beneficial for imaging the breast, peripheral blood vessels, and musculoskeletal injuries. Future development of real-time spatial compound imaging will help address the bulk of general imaging applications by extending this technology to curved array transducers, tissue harmonics, panoramic imaging, and three-dimensional sonography.     

Magnetic resonance imaging of changes elicited by status epilepticus in the rat brain: diffusion-weighted and T2-weighted images,regional blood volume maps,and direct correlation with tissue and cell damage

The rat brain was investigated with structural and functional magnetic resonance imaging (MRI) 12 h after the arrest of pilocarpine-induced status epilepticus lasting 4 h. Histopathological data, obtained immediately after MRI analysis, were correlated with the images through careful evaluation of tissue shrinkage. Diffusion-weighted and T2-weighted imaging showed changes throughout the cerebral cortex, hippocampus, amygdala, and medial thalamus. However, only T2-weighted imaging, based on rapid acquisition relaxation-enhanced sequences, revealed in the cortex inhomogeneous hyperintensity that was highest in a band corresponding to layer V. Regional cerebral blood volume (rCBV) maps were generated using T2*-weighted gradient-echo images and an ultrasmall superparamagnetic iron oxide contrast agent. In the cortex, rCBV peaked in superficial and deep bands exhibiting a distribution complementary to the highest T2-weighted intensity. Selective rCBV increase was also documented in the hippocampus and subcortical structures. In tissue sections, alterations indicative of marked edema were found with Nissl staining in areas corresponding to the highest T2-weighted intensity. Degenerating neurons, revealed by FluoroJadeB histochemistry, were instead concentrated in tissue exhibiting hyperperfusion in rCBV maps, such as hippocampal subfields and dentate gyrus, cortical layers II/III and VI, and medial thalamus. The data indicate that:(i) T2-weighted imaging provides a sensitive tool to investigate edematous brain alterations that follow sustained seizures; (ii) rCBV maps reveal regional hyperperfusion; (iii) rCBV peaks in tissue exhibiting marked neurodegeneration, which may not be selectively revealed by structural MRI. The findings provide an interpretation of the brain response to sustained seizures revealed in vivo by different strategies of MRI analysis.     

食管肿瘤扩散加权成像序列参数优化及相关影像病理对照研究

目的探讨食管肿瘤磁共振扩散成像的技术可行性和b值的选择,比较扩散成像与食管钡餐造影、CT、T2WI在显示病变长度方面的差异.方法食管肿瘤32例,进行常规MRI及DWI横断面扫描b=200、300、500、800、1000s/mm2,分别测定图像SIR和CNR并与常规T2WI图像进行比较.测量食管肿瘤病变的扩散信号强度,分别计算ADC值,选择合适的b值.在DWI图像上测量病变长度,与食管钡餐造影、CT、T2WI及手术切除病理大体标本显示的病变长度进行比较.结果不同b值DWI图像与常规T2WI比较,SIR无显著性差异(P＞0.05),b值为200、300、500 s/mm2时,DWI图像CNR与T2WI有显著性差异(P＜0.05).b值200、300、500 s/mm2DWI图像的SIR和CNR与b值选择800、1000s/mm2时有显著性差异(P＜0.05),b值选择500 s/mm2较为合适.b值500 s/mm2磁共振扩散加权图像显示病变长度与病理结果、食管钡餐造影及T2WI图像无显著性差异(P＞0.05).结论应用8通道阵列线圈结合ASSET技术一次屏气扫描,b值采用500 s/mm2可以获得较为满意的食管肿瘤扩散图像,DWI测量的病变长度与手术切除病理大体标本无显著性差异;DWI与钡餐造影和MRI T2WI在显示病变长度方面有较好的对应关系.     

Sonographic,magnetic resonance imaging,and mammographic assessments of preoperative size of breast cancer.

High resolution sonographic (39 cases), magnetic resonance imaging (32 cases), and mammographic (35 cases) measurements of preoperative size of breast cancer were correlated with the pathologic size in 39 patients with breast carcinoma to determine the most accurate imaging technique for breast cancer size. There were nine T1, 21 T2, four T3, and four T4 tumors. Sonographic and magnetic resonance imaging measurements of tumor size demonstrated correlation coefficients of 0.92 and 0.93, respectively, both of which were superior to that of mammography (0.84). Sonographic tumor size evaluation thus is shown to be equivalent to magnetic resonance imaging in this study. Three of nine (33%), four of seven (57%), and four of eight (50%) T1 tumors would have been overstaged by ultrasonography, magnetic resonance imaging, and mammography, respectively. Three of 21 (14.3%), one of 16 (6.3%), and two of 18 (11.1%) T2 tumors would have been understaged by ultrasonography, magnetic resonance imaging, and mammography, respectively. We therefore found ultrasonography to be of value in the diagnosis and staging of breast cancer.     

Conventional imaging and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography for predicting the clinical outcome of previously treated non-Hodgkin's lymphoma patients.

PURPOSE: The aim of this study was to determine the impact of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) and combined conventional imaging on clinical stage and their ability to predict the clinical outcome of previously treated lymphoma patients. PROCEDURES: Seventy-eight patients with Non-Hodgkin's Lymphoma (NHL) were studied with PET within a median interval of 5.3 months after treatment. Conventional imaging performed after treatment and within three months before PET included 3.3+/-1.3 imaging tests/patient. To determine the independent ability of PET for predicting clinical outcome, PET images were re-read in a blinded fashion. Study endpoints were disease-free survival, or clinical evidence of disease or death. RESULTS: PET downstaged 18 patients, upstaged nine and revealed the same stage as conventional imaging in 51 patients. Using the clinical outcome as gold standard, the positive and negative predictive values of PET were 95% and 83% versus 72% and 67% for conventional imaging (P<0.05). The prognostic accuracy of PET was superior to that of conventional imaging (90 vs. 71%; P<0.05). Kaplan-Meier analysis for disease-free survival showed a significant difference between PET negative and PET positive results (P<0.0001). CONCLUSION: Whole-body FDG-PET imaging modified the clinical stage in 35% of lymphoma patients who were reevaluated after treatment. Moreover, FDG-PET predicted patient outcome with a higher predictive accuracy than conventional imaging. This superior prognostic accuracy was achieved with a single FDG-PET study versus multiple conventional imaging procedures/patient.     

2D-MRCP、3D-MRCP及2D-FIESTA序列诊断胆总管结石

目的探讨2D-MRCP、3D-MRCP和2D-FIESTA在胆总管结石症诊断中的应用价值。方法分析50例经临床手术证实的胆总管结石的2D-MRCP、3D-MRCP和2D-FIESTA序列的MR表现。结果50例中2D-MRCP发现胆总管结石44例(88.00%),检出结石54枚(54/68,79.41%);2D-MRCP结合3D-MRCP发现46例(92.00%),检出结石61枚(61/68,89.71%);2D-MRCP、3D-MRCP结合2D-FIESTA序列发现49例(98.00%),检出结石67枚(67/68,98.53%)。结论2D-MRCP、3D-MRCP结合2D-FIESTA序列对胆总管结石诊断有重要作用。     

Comparison of an 18F labeled derivative of vasoactive intestinal peptide and 2-deoxy-2-[18F]fluoro-D-glucose in nude mice bearing breast cancer xenografts.

PURPOSE: A 18fluorine-labeled derivative of vasoactive intestinal peptide [18F- Arg,Arg VIP(18F-dVIP)] was evaluated as a potential imaging agent for breast cancer by comparison with 2-deoxy-2-[18F]fluoro-D-glucose (FDG) using standard ex vivo determinations and small animal position emission tomography (PET) imaging. PROCEDURES: Human breast carcinomas, T-47D and MDA-MB231, tumor-bearing nude mice were injected intravenously with 18F-dVIP or FDG for imaging and/or biodistribution (ex vivo) determined by gamma counting. RESULTS: FDG had two- to three-fold greater tumor accumulation and target-to-non target contrast relative to 18F-dVIP. VIP receptors were detected in both tumor types but in low concentrations (<15,000 receptors/cell) consistent with lower uptakes. FDG was cleared rapidly from non-target tissues while 18F-dVIP cleared into the kidneys. CONCLUSIONS: 18F-dVIP uptake in mice T-47D tumors and kidneys determined by imaging correlated with values determined by ex vivo counting suggesting that tumor and other tissue uptakes can be quantified by in vivo positron projection imaging.     

Magnetic resonance imaging of the hand, wrist, and forearm: utility in patients with pain and dysfunction as a result of trauma.

We reviewed the clinical data, results of imaging studies, and surgical-pathologic correlations in 41 consecutive patients with pain in the hand, wrist, or forearm to evaluate the role of magnetic resonance imaging in comparison with that of other imaging techniques. Of the 41 patients, 24 had a trauma-related lesion. In 18 of these 24 patients, the findings on magnetic resonance imaging were equivalent to (6 cases) or better than (12 cases) the clinical findings or the findings on other imaging studies for the detection of lesions of the hand, wrist, or forearm. Moreover, the results of magnetic resonance imaging affected the clinical management in 7 of the 24 cases (29%).     

Proceedings of the World Molecular Imaging Congress 2015, Honolulu,Hawaii, September 2-5, 2015: General Abstracts

Due to their remarkable selectivity and specificity for cancer biomarkers, immunoconjugates have emerged as extremely promising vectors for the delivery of diagnostic radioisotopes and fluorophores to malignant tissues. Paradoxically, however, these tools for precision medicine are synthesized in a remarkably imprecise way. Indeed, the vast majority of immunoconjugates are created via the random conjugation of bifunctional probes (e.g., DOTA-NCS) to amino acids within the antibody (e.g., lysines). Yet antibodies have multiple copies of these residues throughout their macromolecular structure, making control over the location of the conjugation reaction impossible. This lack of site specificity can lead to the formation of poorly defined, heterogeneous immunoconjugates with suboptimal in vivo behavior. Over the past decade, interest in the synthesis and development of site-specifically labeled immunoconjugates—both antibody-drug conjugates as well as constructs for in vivo imaging—has increased dramatically, and a number of reports have suggested that these better defined, more homogeneous constructs exhibit improved performance in vivo compared to their randomly modified cousins. In this two-part review, we seek to provide an overview of the various methods that have been developed to create site-specifically modified immunoconjugates for positron emission tomography, single photon emission computed tomography, and fluorescence imaging. We will begin with an introduction to the structure of antibodies and antibody fragments. This is followed by the core of the work: sections detailing the four different approaches to site-specific modification strategies based on cysteine residues, glycans, peptide tags, and unnatural amino acids. These discussions will be divided into two installments: cysteine residues and glycans will be detailed in Part 1 of the review, while peptide tags and unnatural amino acids will be addressed in Part 2. Ultimately, we sincerely hope that this review fosters interest and enthusiasm for site-specific immunoconjugates within the nuclear medicine and molecular imaging communities.     

Artificial intelligence-augmented,label-free molecular imaging method for tissue identification,cancer diagnosis,and cancer margin detection

Label-free high-resolution molecular and cellular imaging strategies for intraoperative use are much needed, but not yet available. To fill this void, we developed an artificial intelligence-augmented molecular vibrational imaging method that integrates label-free and subcellular-resolution coherent anti-stokes Raman scattering (CARS) imaging with real-time quantitative image analysis via deep learning (artificial intelligence-augmented CARS or iCARS). The aim of this study was to evaluate the capability of the iCARS system to identify and differentiate the parathyroid gland and recurrent laryngeal nerve (RLN) from surrounding tissues and detect cancer margins. This goal was successfully met.     

Characterization of a cannabinoid CB2 receptor-selective agonist, A-836339 [2,2,3,3-tetramethyl-cyclopropanecarboxylic acid [3-(2-methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide], using in vitro pharmacological assays, in vivo pain models, and pharmacological magnetic resonance imaging

Studies demonstrating the antihyperalgesic and antiallodynic effects of cannabinoid CB(2) receptor activation have been largely derived from the use of receptor-selective ligands. Here, we report the identification of A-836339 [2,2,3,3-tetramethyl-cyclopropanecarboxylic acid [3-(2-methoxy-ethyl)-4,5-dimethyl-3H-thiazol-(2Z)-ylidene]-amide], a potent and selective CB(2) agonist as characterized in in vitro pharmacological assays and in in vivo models of pain and central nervous system (CNS) behavior models. In radioligand binding assays, A-836339 displays high affinities at CB(2) receptors and selectivity over CB(1) receptors in both human and rat. Likewise, A-836339 exhibits high potencies at CB(2) and selectivity over CB(1) receptors in recombinant fluorescence imaging plate reader and cyclase functional assays. In addition A-836339 exhibits a profile devoid of significant affinity at other G-protein-coupled receptors and ion channels. A-836339 was characterized extensively in various animal pain models. In the complete Freund's adjuvant model of inflammatory pain, A-836339 exhibits a potent CB(2) receptor-mediated antihyperalgesic effect that is independent of CB(1) or mu-opioid receptors. A-836339 has also demonstrated efficacies in the chronic constrain injury (CCI) model of neuropathic pain, skin incision, and capsaicin-induced secondary mechanical hyperalgesia models. Furthermore, no tolerance was developed in the CCI model after subchronic treatment with A-836339 for 5 days. In assessing CNS effects, A-836339 exhibited a CB(1) receptor-mediated decrease of spontaneous locomotor activities at a higher dose, a finding consistent with the CNS activation pattern observed by pharmacological magnetic resonance imaging. These data demonstrate that A-836339 is a useful tool for use of studying CB(2) receptor pharmacology and for investigation of the role of CB(2) receptor modulation for treatment of pain in preclinical animal models.     

Microparticle-Based Molecular MRI of Atherosclerosis, Thrombosis, and Tissue Ischemia

MRI is well suited for imaging vascular disease as it provides excellent soft tissue contrast and spatial resolution of the vessel wall. By generating potent contrast effects, iron oxide particles further enhance the ability of MRI to deliver functional information in a range of vascular syndromes. Larger microparticles of iron oxide (MPIO) generate sufficient contrast to enable detection of low-abundance vascular targets in vivo. Ligand-conjugated MPIO confer molecular specificity, facilitating molecular imaging of a range of specific endovascular targets. This review discusses the application of iron oxide particles in the molecular imaging of a variety of vascular syndromes. In particular, ligand-conjugated MPIO have been used for targeted molecular imaging in experimental models of atherosclerosis, thrombosis, and tissue ischemia syndromes. This provides a platform for vascular molecular imaging that could accelerate diagnosis, characterize disease progression, and measure response to treatment in a clinical setting.     

Reproducibility of BOLD, perfusion, and CMRO2 measurements with calibrated-BOLD fMRI

The coupling of changes in cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO(2)) during brain activation can be characterized by an empirical index, n, defined as the ratio between fractional CBF change and fractional CMRO(2) change. The combination of blood oxygenation level dependent (BOLD) imaging with CBF measurements from arterial spin labeling (ASL) provides a potentially powerful experimental approach for measuring n, but the reproducibility of the technique previously has not been assessed. In this study, inter-subject variance and intra-subject reproducibility of the method were determined. Block design %BOLD and %CBF responses to visual stimulation and mild hypercapnia (5% CO(2)) were measured, and these data were used to compute the BOLD scaling factor M, %CMRO(2) change with activation, and the coupling index n. Reproducibility was determined for three approaches to defining regions-of-interest (ROIs): 1) Visual area V1 determined from prior retinotopic maps, 2) BOLD-activated voxels from a separate functional localizer, and 3) CBF-activated voxels from a separate functional localizer. For estimates of %BOLD, %CMRO(2) and n, intra-subject reproducibility was found to be best for regions selected according to CBF activation. Among all fMRI measurements, estimates of n were the most robust and were substantially more stable within individual subjects (coefficient of variation, CV=7.4%) than across the subject pool (CV=36.9%). The stability of n across days, despite wider variability of CBF and CMRO(2) responses, suggests that the reproducibility of blood flow changes is limited by variation in the oxidative metabolic demand. We conclude that the calibrated BOLD approach provides a highly reproducible measurement of n that can serve as a useful quantitative probe of the coupling of blood flow and energy metabolism in the brain.     

In Vivo Follow-up of Rat Tumor Models with 2-Deoxy-2-[F-18]fluoro-d-glucose/Dual-Head Coincidence Gamma Camera Imaging

Before studying the impact of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) imaging with a dual-head coincidence gamma camera (DHC) for the follow-up of animal tumor models, we wanted to optimize this technique.Methods Three different animal tumor models (osteosarcoma, melanoma, and breast cancer) were studied after FDG injection. Dynamic and dual time point FDG/DHC imaging were studied from one hour to five hours postinjection. In vitro tumor cell FDG uptake was assessed in eight different tumor cell lines. In one model (osteosarcoma), tumor growth, lung metastasis emergence, and survival were assessed by classical clinical follow-up and compared to FDG imaging in a control group (n = 6) and in a group treated by endostatin liposome complexes (n = 6).Results Images obtained five hours after injection were more reliable for tumor growth follow-up than standard images (one hour). In vitro tumor cell FDG uptake confirmed in vivo imaging studies. In eight different tumor cell lines the FDG uptake was higher after five hours incubation than after one hour (p < 0.002). With FDG follow-up, we found that FDG uptake was strongly correlated with survival and that lung metastasis larger than 5 mm could be detected.Conclusion Using the optimization proposed above, DHC/FDG functional imaging seems to be a powerful tool to study rat tumor models and to help develop novel cancer therapies.