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BACKGROUND AND PURPOSE: Efficient detection of metastases is important for patient’ treatment. This prospective study was to explore the clinical value of contrast-enhanced T2 FLAIR in imaging brain metastases using half-dose gadobenate dimeglumine. MATERIALS AND METHODS: In vitro signal intensity of various gadolinium concentrations was explored by spin-echo T1-weighted imaging and T2 FLAIR. Then, 46 patients with lung cancer underwent nonenhanced T2 FLAIR before administration of half-dose gadobenate dimeglumine and 3 consecutive contrast-enhanced T2 FLAIR sequences followed by 1 spin-echo T1WI after administration of half-dose gadobenate dimeglumine. After an additional dose of 0.05 mmol/kg, 3D brain volume imaging was performed. All brain metastases were classified as follows: solid-enhancing, ≥ 5 mm (group A); ring-enhancing, ≥ 5 mm (group B); and lesion diameter of

Aberrant metabolism is a key factor in many neurological disorders. The ability to measure such metabolic impairment could lead to improved detection of disease progression, and development and monitoring of new therapeutic approaches. Hyperpolarized 13C magnetic resonance spectroscopy (MRS) is a developing imaging technique that enables non-invasive measurement of enzymatic activity in real time in living organisms. Primarily applied in the fields of cancer and cardiac disease so far, this metabolic imaging method has recently been used to investigate neurological disorders. In this review, we summarize the preclinical research developments in this emerging field, and discuss future prospects for this exciting technology, which has the potential to change the clinical paradigm for patients with neurological disorders.

Genetically encoded fluorescent indicators, combined with optical imaging, enable the detection of physiologically or behaviorally relevant neural activity with high spatiotemporal resolution. Recent developments in protein engineering and screening strategies have improved the dynamic range, kinetics, and spectral properties of genetically encoded fluorescence indicators of brain chemistry. Such indicators have detected neurotransmitter and calcium dynamics with high signal-to-noise ratio at multiple temporal and spatial scales in vitro and in vivo. This review summarizes the current trends in these genetically encoded fluorescent indicators of neurotransmitters and calcium, focusing on their key metrics and in vivo applications.

Imaging is an indispensable tool for brain tumour diagnosis, surgical planning, and follow-up. Definite diagnosis, however, often demands histopathological analysis of microscopic features of tissue samples, which have to be obtained by invasive means. A non-invasive alternative may be to probe corresponding microscopic tissue characteristics by MRI, or so called 'microstructure imaging'. The promise of microstructure imaging is one of 'virtual biopsy' with the goal to offset the need for invasive procedures in favour of imaging that can guide pre-surgical planning and can be repeated longitudinally to monitor and predict treatment response. The exploration of such methods is motivated by the striking link between parameters from MRI and tumour histology, for example the correlation between the apparent diffusion coefficient and cellularity. Recent microstructure imaging techniques probe even more subtle and specific features, providing parameters associated to cell shape, size, permeability, and volume distributions. However, the range of scenarios in which these techniques provide reliable imaging biomarkers that can be used to test medical hypotheses or support clinical decisions is yet unknown. Accurate microstructure imaging may moreover require acquisitions that go beyond conventional data acquisition strategies. This review covers a wide range of candidate microstructure imaging methods based on diffusion MRI and relaxometry, and explores advantages, challenges, and potential pitfalls in brain tumour microstructure imaging.

Electroencephalogram (EEG) has evolved to be a well-established tool for imaging brain activity. This progress is mainly due to the development of high-resolution (HR) EEG methods. One class of HR-EEG is the cortical potential imaging (CPI), which aims to estimate the potential distribution on the cortical surface, which is much more informative than EEG. Even though these methods exhibit good performance, most of them have inherent inaccuracies that originate from their operating principles that constrain the solution or require a complex calculation process. The back-projection CPI (BP-CPI) method is relatively new and has the advantage of being constraint-free and computation inexpensive. The method has shown relatively good accuracy, which is necessary to become a clinical tool. However, better performance must be achieved. In the present study, two improvements are proposed. Both are embedded as adjacent stages to the BP-CPI and are based on the multi-resolution optimization approach (MR-CPI). A series of Monte-Carlo simulations were performed to examine the characteristics of the proposed improvements. Additional tests were done, including different EEG noise levels and variation in electrode-numbers. The results showed highly accurate cortical potential estimations, with a reduction in estimation error by a factor of 3.75 relative to the simple BP-CPI estimation error. We also validated these results with true EEG data. Analyzing these EEGs, we have demonstrated the MR-CPI competence to correctly localize cortical activations in a real environment. The MR-CPI methods were shown to be reliable for estimating cortical potentials, enabling researchers to obtain fast and robust high-resolution EEGs.

We will discuss the developments in TSPO PET imaging and the contribution this technique has had to understanding neuroinflammation in vivo, as well as the limitations inherent to the currently available radioligands and the potential future direction. Positron emission tomography (PET) imaging targeting the translocator protein 18 kDa (TSPO) has led to major advances in understanding the pathological role played by microglia activation and neuroinflammation in a diverse range of neurodegenerative conditions. The first-generation radioligand 11[C](R)-PK11195 has been the most widely studied and has led to considerable advancements in defining the role of neuroinflammation in neuronal degeneration and dysfunction. However, limitations including low signal-to-noise ratio and high nonspecific binding have led to the development of new TSPO-specific radioligands in an attempt to improve the quality of TSPO imaging. Unfortunately, these new radioligands have not been without their own problems, and the expected improvement in image quality has not been achieved.

The development of reversibly binding radioligands for imaging brain proteins in vivo, such as enzymes, neurotransmitter transporters, receptors and ion channels, with positron emission tomography (PET) is keenly sought for biomedical studies of neuropsychiatric disorders and for drug discovery and development, but is recognized as being highly challenging at the medicinal chemistry level. This article aims to compile and discuss the main considerations to be taken into account by chemists embarking on programs of radioligand development for PET imaging of brain protein targets.

PURPOSE There is a need for an alternative PET probe, which does not show normal brain tissue uptake in the evaluation of metastasis to the brain. Therefore, we investigate the feasibility of F-labeled glutamine analog, F-(2S,4R)-4-fluoroglutamine (F-FGln), as a new metabolic probe to detect brain metastasis. METHODS Patients (7 men and 7 women; age, 25-67 years) with suspected brain metastasis were enrolled for this study. All patients were imaged first with F-FGln PET (3 patients for 1-hour dynamic whole-body PET/CT scans, and 11 patients for static whole-body scans at 30 ± 10 minutes after injection), followed by a whole-body F-FDG PET performed in the same week. The characteristics of F-FGln PET imaging in brain metastasis patients were compared with that of F-FDG PET and/or contrast-enhanced MRI patient-by-patient. A composite of all functional and anatomic imaging studies served as the imaging comparator. RESULTS Initial study in 3 patients using 1-hour dynamic scan showed that 30 ± 10 minutes after injection is optimal for identifying brain metastasis with a high-contrast ratio. All patients were positive for brain metastasis on this studies that demonstrated 38 lesions in 6 anatomic regions on the imaging comparator. The per-lesion detection rates for F-FGln PET and F-FDG PET were 81.6% and 36.8%, respectively. The average tumor-to-normal brain ratio of F-FGln PET was significantly better than that of F-FDG PET in all patients (4.97 ± 2.23 vs 1.22 ± 0.69, P < 0.05). Furthermore, our results suggest that F-FGln uptake in brain metastasis appeared to be independent of tumor size and peripheral edema. In addition, in 14 brain metastatic lesions visualized by both F-FDG PET and F-FGln PET imaging, a positive correlation of SUVmax was observed (r = 0.780, P < 0.01). As to the extracranial metastasis, both tracers showed a concordant increased radioactive uptake except in liver and bone. CONCLUSIONS The initial imaging of F-FGln presenting a promising new PET radiotracer for patients with brain metastasis and its utility in the liver and bone metastatic lesions may require more caution due to uptake in normal structures.

In this review, we discuss molecular brain imaging studies using positron emission tomography (PET) with 2-deoxy-2(18F)fluoro-d-glucose (FDG) in human newborns and infants, and illustrate how this technology can be applied to probe the neuropathophysiology of neonatal neurologic disorders. PET studies have been difficult to perform in sick babies because of patient transportation issues and suboptimal spatial resolution. With approval from the FDA and the institutional review board, we modified and installed the Focus 220 animal microPET scanner (Concorde Microsystems, Knoxville, TN) directly in our neonatal intensive care unit in Children’s Hospital of Michigan and verified the high spatial resolution (Areceptors (using11C-flumazenil) in newborns also show a pattern very different from adults, with high binding in amygdala-hippocampus, sensory-motor cortex, thalamus, brain stem, and basal ganglia, in that order. We speculate that the early development of amygdala/hippocampus prepares the baby for bonding, attachment, and memory, and the deprivation of such experiences during a sensitive period results in malfunction of these networks and psychopathology, as has been shown in studies on severely socioemotionally deprived children. Recently developed hybrid PET/magnetic resonance (MR) scanners allow the simultaneous acquisition of PET and MR data sets with advanced applications. These devices are particularly advantageous for scanning babies and infants because of the high spatial resolution, automated coregistration of anatomical and functional images and, in the case of need for sedation, maximal data acquired in 1 session.

BACKGROUND: DPD scintigraphy has been advocated for imaging cardiac amyloid in ATTR amyloidosis. PET utilizing (11)C-Pittsburgh compound B (PIB) is the gold standard for imaging brain amyloid in Alzheimer's disease. PIB was recently shown to identify cardiac amyloidosis in both AL and ATTR amyloidosis. In the ATTR population, two types of amyloid fibrils exist, one containing fragmented and full-length TTR (type A) and the other only full-length TTR (type B). The aim of this study was to further evaluate PIB-PET in patients with hereditary ATTR amyloidosis. METHODS: Ten patients with biopsy-proven V30M ATTR amyloidosis and discrete or no signs of cardiac involvement were included. Patients were grouped according to TTR-fragmentation. All underwent DPD scintigraphy, echocardiography, and PIB-PET. A left ventricular PIB-retention index (PIB-RI) was established and compared to five normal volunteers. RESULTS: PIB-RI was increased in all patients (P

SUMMARY: In many pathophysiologic situations, including brain neoplasms, neurodegenerative disease, and chronic and acute ischemia, an imbalance exists between oxygen tissue consumption and delivery. Furthermore, oxygenation changes following a stress challenge, such as with carbogen gas or acetazolamide, can yield information about cerebrovascular reactivity. The unique sensitivity of the BOLD effect to the presence of deoxyhemoglobin has led to its widespread use in the field of cognitive neurosciences. However, the high spatial and temporal resolution afforded by BOLD imaging does not need to be limited to the study of healthy brains. While the complex relationship between the MR imaging signal and tissue oxygenation hinders a direct approach, many different methods have been developed during the past decade to obtain specific oxygenation measurements. These include qBOLD, phase- and susceptibility-based imaging, and intravascular T2-based approaches. The aim of this review is to give an overview of the theoretic basis of these methods as well as their application to measure oxygenation in both healthy subjects and those with disease.

The past 15 years has seen a rapid expansion in the number of studies using neuroimaging techniques to investigate maturational changes in the human brain. In this paper, I review MRI studies on structural changes in the developing brain, and fMRI studies on functional changes in the social brain during adolescence. Both MRI and fMRI studies point to adolescence as a period of continued neural development. In the final section, I discuss a number of areas of research that are just beginning and may be the subject of developmental neuroimaging in the next twenty years. Future studies might focus on complex questions including the development of functional connectivity; how gender and puberty influence adolescent brain development; the effects of genes, environment and culture on the adolescent brain; development of the atypical adolescent brain; and implications for policy of the study of the adolescent brain.

In this review focus is on structural imaging in the Alzheimer's disease (AD) pre-states, particularly cognitively normal (CN) persons at future dementia risk. Findings in mild cognitive impairment (MCI) are described here only for comparison with CN. Cited literature evidence and commentary address issues of structural imaging alterations in CN that precede MCI and AD, regional patterns of such alterations, and the time relationship between structural imaging alterations and the appearance of symptoms of AD, issues relevant to the conduct of future AD prevention trials. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

The oxygen element is one of the most important components for life on earth because various oxygen containing molecules are present in all levels of biological systems, and oxygen accounts for two thirds of the total human body mass and 90% of the mass of water. However, in vivo oxygen-17 (17O) NMR has received very little attention compared to other in vivo NMR methodologies, such as 1H, 13C and 31P NMR; even though the 17O NMR signal was first observed in 1951 [1] and utilized since then for many chemical and biochemical applications (see a recent review by Gerothanassis [2, 3] and the cited references therein). It has been demonstrated that in vivo 17O NMR can be used to monitor the uptake or washout of an 17O-labeled exogenous agent (e.g. 17O-labeled water) for studying tissue perfusion [4–7] or for detecting oxygen-containing metabolites in living species [8–10]. Nevertheless, the most valuable and unique capability of in vivo 17O NMR is to non-invasively determine the metabolic rate of oxygen in live animals or humans (see [11–13] and references cited therein). In this review article, we attempt to provide an overview of the methodology background and the present status of in vivo 17O MR spectroscopy (MRS)/imaging (MRI) approach for imaging the cerebral metabolic rate of oxygen (CMRO2) and studying the central roles of cerebral oxygen metabolism in brain function. The challenges and potentials of this 17O-MR based CMRO2 imaging method will also be discussed.

The development of new MRI techniques in the last two decades has provided neuroradiologists and neurosurgeons with additional noninvasive imaging tools for management and treatment of brain tumors. When coupled with standard structural MR sequences in imaging brain tumors, Blood Oxygenation Level Dependent (BOLD) functional MRI (fMRI), Perfusion Weighted Imaging (PWI) and Diffusion Tensor Imaging (DTI) provide additional physiologic information that is very useful for differential diagnosis, presurgical planning and prognosis. In this review after a brief technical description of BOLD fMRI, PWI and DTI, studies are described from the literature that have extensively validated these imaging techniques in comparison with invasive “gold standard” techniques such as intraoperative electrical cortical and subcortical stimulation mapping or biopsy. Additional studies are mentioned that demonstrate the positive impact of BOLD fMRI, PWI and DTI on brain tumor treatment and clinical outcome. In the final section an interesting clinical case treated at our institution is presented that highlights the clinical utility of this integrated physiologic brain tumor imaging approach.

Significant advances in anatomical and functional neuroimaging techniques have allowed researchers and clinicians to visualize the brain in action. The field of neuroimaging currently includes newer and faster scanners, improved image quality, higher spatial and temporal resolution and diverse methods of acquisition and analysis. Beyond simply imaging brain structures, these developments enable quantitative assessment of the microstructural and functional architecture, perfusion and metabolism of the brain. The resultant highly granular data have the potential to greatly improve characterization of neurological, neurosurgical and psychiatric disorders without invasive neurosurgery. However, the surge in neuroimaging data that can be collected over a relatively short acquisition period has led to a “big data” problem, where novel methods are needed to appropriately extract and analyze information and integrate data with other types of big data, such as genomic and proteomic data. Another challenge is the translation of these new technologies from basic science into clinical practice, so that they can be leveraged to improve patient outcomes and alleviate human disease. Critical to this endeavor is research comparing the effectiveness and outcomes of these advancements to allow widespread acceptance in the modern, economically constrained healthcare system. This review aims to illustrate the different facets of cutting edge neuroimaging techniques, as well as the potential role of these methods as clinical tools for evaluating the breadth of diseases that affect the brain.

Neurobiological development is a complex process that originates at conception and extends throughout the lifespan (Casey, Tottenham, Liston, & Durston, 2005; Cicchetti & Cannon, 1999; Nowakowski, 1987; Rakic, 1996; Thompson & Nelson, 2001). The course of brain development can be altered by a host of factors, ranging from genetic liabilities to psychosocial stressors, and mental disorders are thought to eventuate from etiologic factors that modify the normal progression of brain development.

Positron emission tomography (PET) molecular imaging of brain targets is a powerful tool to diagnose, follow up, and develop treatments and personalized medicine for a number of acute and chronic brain disorders. The availability of β+ emitter tracers labelled with [(11)C] or [(18)F] having optimal characteristics of affinity and selectivity for alpha-7 nicotinic receptors (α7R) has received considerable attention, due to the major implication of these receptors in brain functions. The aim of this review is to identify the interest and need for the in vivo exploration of α7R by PET molecular imaging, which tools are currently available for this and how to progress.

Combining electroencephalogram (EEG) recording and functional magnetic resonance imaging (fMRI) offers the potential for imaging brain activity with high spatial and temporal resolution. This potential remains limited by the significant ballistocardiogram (BCG) artifacts induced in the EEG by cardiac pulsation-related head movement within the magnetic field. We model the BCG artifact using a harmonic basis, pose the artifact removal problem as a local harmonic regression analysis, and develop an efficient maximum likelihood algorithm to estimate and remove BCG artifacts. Our analysis paradigm accounts for time-frequency overlap between the BCG artifacts and neurophysiologic EEG signals, and tracks the spatiotemporal variations in both the artifact and the signal. We evaluate performance on: simulated oscillatory and evoked responses constructed with realistic artifacts; actual anesthesia-induced oscillatory recordings; and actual visual evoked potential recordings. In each case, the local harmonic regression analysis effectively removes the BCG artifacts, and recovers the neurophysiologic EEG signals. We further show that our algorithm outperforms commonly used reference-based and component analysis techniques, particularly in low SNR conditions, the presence of significant time-frequency overlap between the artifact and the signal, and/or large spatiotemporal variations in the BCG. Because our algorithm does not require reference signals and has low computational complexity, it offers a practical tool for removing BCG artifacts from EEG data recorded in combination with fMRI., National Institutes of Health (U.S.) (Award DP1-OD003646), National Institutes of Health (U.S.) (Award TR01-GM104948), National Institutes of Health (U.S.) (Grant R44NS071988), National Institute of Neurological Diseases and Stroke (U.S.) (Grant Grant R44NS071988)

Adversity early in life can disrupt the functioning of the hypothalamic-pituitary-adrenal axis (HPAA) and increase risk for negative health outcomes. Recent research suggests that cortisol in scalp hair represents a promising measure of HPAA function. However, little is known about the relationship between early exposure to traumatic events and hair cortisol concentrations (HCC) in childhood, a critical period of HPAA development. The current study measured HCC in scalp hair samples collected from 70 community-based children (14 males, mean age=9.50) participating in the Imaging Brain Development in the Childhood to Adolescence Transition Study (iCATS). Data were also collected on lifetime exposure to traumatic events and current depressive symptoms. Lifetime exposure to trauma was associated with elevated HCC; however, HCC was not associated with current depressive symptoms. Consistent with some prior work, males were found to have higher HCC than females, although results should be treated with caution due to the small number of males who took part. Our findings suggest that hair cortisol may represent a biomarker of exposure to trauma in this age group; however, further study is necessary with a particular focus on the characterization of trauma and other forms of adversity.

The development of a noninvasive method to detect early, subtle changes in the brains of patients with Alzheimer's disease (AD) would have considerable clinical value as therapy. This therapy is most likely to be successful if intervention could occur before neurons were irreversibly damaged or lost. An ideal biological neuroimaging marker would be an early, sensitive, and valid indicator of brain changes, capable of discriminating the effects of normal aging. The introduction of high field-strength clinical magnetic resonance imaging (MRI) systems now offer a powerful new noninvasive tool that may be capable of detecting brain pathology resulting from AD. Here we present results from high field-strength MRI in transgenic mice along with a new MRI technique for imaging brain iron. The successful translation of this research to the clinic could prove important to both the early diagnosis and monitoring of the efficacy of potential therapies in humans.

This article describes experimental studies performed to demonstrate the feasibility of BOLD fMRI using echo-planar imaging (EPI) at 7 T and to characterize the BOLD response in humans at this ultrahigh magnetic field. Visual stimulation studies were performed in normal subjects using high-resolution multishot EPI sequences. Changes in R(*)(2) arising from visual stimulation were experimentally determined using fMRI measurements obtained at multiple echo times. The results obtained at 7 T were compared to those at 4 T. Experimental data indicate that fMRI can be reliably performed at 7 T and that at this field strength both the sensitivity and spatial specificity of the BOLD response are increased. This study suggests that ultrahigh field MR systems are advantageous for functional mapping in humans. Magn Reson Med 45:588-594, 2001.

Using positron emission tomography (PET), we measured the relative changes in regional cerebral metabolic rate of glucose (rCMRglc) during 2 Hz repetitive transcranial magnetic stimulation (rTMS) of the left sensorimotor cortex (SM1) and during imitation of rTMS-induced arm movements. Such stimulation caused an rCMRglc increase of about 8% within the SM1. The relative rCMRglc increase within SM1 was significantly greater in magnitude and larger in area during voluntary imitation of rTMS-induced arm movements. Moreover, the rostral part of the SMA was significantly more activated by voluntary movements than during rTMS. Combining rTMS and PET has the potential to visualize rTMS-related net brain activation, and may open up new possibilities for functional network analysis by comparing willed brain activation with electromagnetic brain activation.

The imaging of translocator 18 kDa protein (TSPO) in living human brain with radioligands by positron emission tomography (PET) has become an important means for the study of neuroinflammatory conditions occurring in several neuropsychiatric disorders. The widely used prototypical PET radioligand [(11)C](R)-PK 11195 ([(11)C](R)-1; [N-methyl-(11)C](R)-N-sec-butyl-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide) gives a low PET signal and is difficult to quantify, whereas later generation radioligands have binding sensitivity to a human single nucleotide polymorphism (SNP) rs6971, which imposes limitations on their utility for comparative quantitative PET studies of normal and diseased subjects. Recently, azaisosteres of 1 have been developed with improved drug-like properties, including enhanced TSPO affinity accompanied by moderated lipophilicity. Here we selected three of these new ligands (7-9) for labeling with carbon-11 and for evaluation in monkey as candidate PET radioligands for imaging brain TSPO. Each radioligand was readily prepared by (11)C-methylation of an N-desmethyl precursor and was found to give a high proportion of TSPO-specific binding in monkey brain. One of these radioligands, [(11)C]7, the direct 4-azaisostere of 1, presents many radioligand properties that are superior to those reported for [(11)C]1, including higher affinity, lower lipophilicity, and stable quantifiable PET signal. Importantly, 7 was also found to show very low sensitivity to the human SNP rs6971 in vitro. Therefore, [(11)C]7 now warrants evaluation in human subjects with PET to assess its utility for imaging TSPO in human brain, irrespective of subject genotype.

Light can be used to probe the function and structure of human tissues. We have been exploring two distinct methods: (i) externally emitting light into tissue and measuring the transmitted light to characterize a region through which the light has passed, and (ii) internally generating light within tissue and using the radiated light as a quantitative homing beacon. The emitted–light approach falls within the domain of spectroscopy, and has allowed for imaging of intracranial haemorrhage in newborns and of brain function in adults. The generated–light approach is conceptually parallel to positron emission tomography (PET) or nuclear medicine scanning, and has allowed for real–time, non–invasive monitoring and imaging of infection and gene expressionin vivousing low–light cameras and ordinary lenses. In this paper, we discuss recent results and speculate on the applications of such techniques.

Radiolabeled amino acids (AAs) are an important class of imaging agents for PET and SPECT that target the increased levels of AA transport by many tumor cells. System L AA transport has been a major focus of tracer development, and work in this field has led to several tracers that are effective for imaging brain tumors. Emerging data also support the use of certain radiolabeled AAs for neuroendocrine tumors and prostate cancer. Recently, new (18)F-labeled AAs have been developed that target transporters other than system L, including system A, glutamine, xCT, and cationic AA transporters. This review provides an overview of this class of molecular imaging agents and highlights the current status of oncologic imaging with radiolabeled AAs in terms of tracer considerations and key clinical applications.

The need for prompt and detailed evaluation of cancers and their treatment is requiring increasingly sophisticated methodologies for in vivo assessment. Morphological detail as provided by CT and MRI has yielded significant advances in diagnostic medicine. In spite of such advances, the means of achieving the clinical goals of improved quality and quantity of life in many cancer patients remain elusive. It is becoming increasingly evident that only with the addition of complementary physiological and biochemical data will further advances occur. While neither in vivo morphological imaging with CT or MRI nor physiological imaging with PET or MRS can provide the resolution of microscopic or cellular level assessment, all can provide macroscopic or regional data. With PET, however, exploration of the kinetics or chemical processes occurring at the cellular level is providing a "biological resolution" not heretofore achieved with in vivo imaging. Application of this complementary morphological and biochemical diagnostic information will likely lead to significant advances in patient management in the immediate future, most of which would probably not be achievable using any individual technique. Efficacy studies should be performed, however, when introducing any new high-technology methodology into clinical practice. A number of retrospective and prospective trials on PET applications in clinical oncology are ongoing sponsored by organizations such as the Institute for Clinical PET and the Western PET Association. Detailed studies also are underway to estimate the "cost" of delivery of PET services to the community (146). Numerous PET feasibility studies in animal models have demonstrated that no one radiotracer serves as the best agent for tumor imaging in all cases. Such studies with radiolabeled amino acids, sugars, and nucleoside derivatives, representatives of the major classes of biomolecules, have demonstrated variable tumor uptake dependent on such parameters as the type of cancer, organ of origin, animal host, and chemical structure of the radioligand. Detailed analysis of tracer uptake using multiple ligands in a variety of animal tumor models and clinical patients suggests that while given types of cancers may be better imaged with certain radiotracers, the use of multitracer imaging provides the specific details necessary for appropriate interpretation of tumor status. In addition, in cases where the diagnosis is uncertain, such information could have a significant impact on patient management by reducing the diagnostic differential. In spite of the many successes achieved with FDG in brain tumor imaging, the most well-known example of the problems that can arise with PET image interpretation is with the use of this agent.(ABSTRACT TRUNCATED AT 400 WORDS)

To determine the optimal timing for imaging brain tumours and other brain lesions with 18F-labelled fluoromethylcholine (18F-FCho) PET.Dynamic PET imaging with 18F-FCho (acquisition time of 28 min) was performed in 24 patients with space-occupying lesions in the brain. On the coregistered PET and MRI, lesion-to-normal tissue uptake ratios (LNRs) were calculated. Time-activity curves (TACs) were generated on the basis of the LNRs. Changes in LNR over time were calculated on the basis of the linear part of the TAC (last 22 min of the acquisition).TACs for 18F-FCho in gliomas of different grading showed that, after a rapid uptake phase, the mean increase in LNR was 1.07 ± 0.93 for glioblastomas, -0.52 ± 1.56 for anaplastic astrocytomas, 0.04 ± 0.13 for grade 2 oligoastrocytomas and 0.37 in a case of a pilocytic astrocytoma. The average increase in LNR was 0.46 for a brain metastasis, 0.41 ± 0.69 for radiation-induced mass lesions and 1.07 for a tumefactive demyelinating lesion. In contrast, TACs for 18F-FCho in meningiomas showed that, after a rapid uptake phase, the average change in LNR was -5.25 ± 4.19 for typical meningiomas and -3.04 in a case of a mixed angiomatous and clear cell meningioma.On the basis of the TACs, PET imaging with 18F-FCho starting within minutes after the administration of the tracer is preferred for the detection of brain tumours and other brain lesions. If discrimination between meningioma and other brain tumours is of concern, both 'early' and 'late' PET imaging could be helpful.

Although in the last decade brain activation in healthy aging and dementia was mainly studied using task-activation fMRI, there is increasing interest in task-induced decreases in brain activity, termed deactivations. These deactivations occur in the so-called default mode network (DMN). In parallel a growing number of studies focused on spontaneous, ongoing ‘baseline’ activity in the DMN. These resting state fMRI studies explored the functional connectivity in the DMN. Here we review whether normal aging and dementia affect task-induced deactivation and functional connectivity in the DMN. The majority of studies show a decreased DMN functional connectivity and task-induced DMN deactivations along a continuum from normal aging to mild cognitive impairment and to Alzheimer's disease (AD). Even subjects at risk for developing AD, either in terms of having amyloid plaques or carrying the APOE4 allele, showed disruptions in the DMN. While fMRI is a useful tool for detecting changes in DMN functional connectivity and deactivation, more work needs to be conducted to conclude whether these measures will become useful as a clinical diagnostic tool in AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease.

The Center for Magnetic Resonance (CMRR) at the University of Minnesota was one of laboratories where the work that simultaneously and independently introduced functional magnetic resonance imaging (fMRI) of human brain activity was carried out. However, unlike other laboratories pursuing fMRI at the time, our work was performed at 4 Tesla magnetic field and coincided with the effort to push human magnetic resonance imaging to field strength significantly beyond 1.5 Tesla which was the high-end standard of the time. The human fMRI experiments performed in CMRR were planned between two colleagues who had known each other and had worked together previously in Bell Laboratories, namely Seiji Ogawa and myself, immediately after the Blood Oxygenation Level Dependent (BOLD) contrast was developed by Seiji. We were waiting for our first human system, a 4 Tesla system, to arrive in order to attempt at imaging brain activity in the human brain and these were the first experiments we performed on the 4 Tesla instrument in CMRR when it became marginally operational. This was a prelude to a subsequent systematic push we initiated for exploiting higher magnetic fields to improve the accuracy and sensitivity of fMRI maps, first going to 9.4 Tesla for animal model studies and subsequently developing a 7 Tesla human system for the first time. Steady improvements in high field instrumentation and ever expanding armamentarium of image acquisition and engineering solutions to challenges posed by ultrahigh fields has brought fMRI to submillimeter resolution in the whole brain at 7 Tesla, the scale necessary to reach cortical columns and laminar differentiation in the whole brain. The solutions that emerged in response to technological challenges posed by 7 Tesla also propagated and continues to propagate to lower field clinical systems, a major advantage of the ultrahigh fields effort that is underappreciated. Further improvements at 7T are inevitable. Further translation of these improvements to lower field clinical systems to achieve new capabilities and to magnetic fields significantly higher than 7 Tesla to enable human imaging is inescapable.

A multimodal optical/paramagnetic nanoprobe, Den-Angio, was developed and demonstrated a capability to circumvent the blood brain barrier (BBB) and visualize brain tumors with high sensitivity in vivo. Den-Angio holds promise to pre-operatively localize brain tumors and make image-guided tumor resection possible during surgery.

We have recently developed a mobile brain imaging method (MoBI), that allows for simultaneous recording of brain and body dynamics of humans actively behaving in and interacting with their environment. A mobile imaging approach was needed to study cognitive processes that are inherently based on the use of human physical structure to obtain behavioral goals. This review gives examples of the tight coupling between human physical structure with cognitive processing and the role of supraspinal activity during control of human stance and locomotion. Existing brain imaging methods for actively behaving participants are described and new sensor technology allowing for mobile recordings of different behavioral states in humans is introduced. Finally, we review recent work demonstrating the feasibility of a MoBI system that was developed at the Swartz Center for Computational Neuroscience at the University of California, San Diego, demonstrating the range of behavior that can be investigated with this method. Copyright © 2011 by Walter de Gruyter, Berlin, Boston.

Magnetic Resonance Spectroscopic Imaging (MRSI) is a technique for imaging spatial variation of metabolites and has been very useful in characterizing biochemical changes associated with disease as well as response to therapy in malignant pathologies. This work presents a self-calibrated undersampling to accelerate 3D elliptical MRSI and an extrapolation-reconstruction algorithm based on the GRAPPA method. The accelerated MRSI technique was tested in three volunteers and five brain tumor patients. Acceleration allowed larger spatial coverage and consequently, less lipid contamination in spectra, compared to fully sampled acquisition within the same scantime. Metabolite concentrations measured from the accelerated acquisitions were in good agreement with measurements obtained from fully sampled MRSI scans.

Brain imaging techniques are assuming a greater range of roles in neuro-oncology. New techniques promise earlier recognition of the spread of tumors to the brain, which is useful in staging of disseminated disease, as well as better definition of small lesions associated with presentations of epilepsy. There is the promise that entirely noninvasive, specific diagnosis of brain tumors may become possible. Imaging methods are being used increasingly to direct and monitor therapy. Preoperative and intraoperative imaging are being used for guiding tumor surgery. An exciting potential goal for greater use of imaging is in the individualization of medical therapies either by analysis of in vitro responses or by visualization of drug responses on the tumor in situ. An important focus for technical development is in the robust integration of complementary information to allow optimization of the sensitivity and specificity of multimodal examinations.

Methods for optimizing the acquisition, reconstruction and analysis of positron emission tomography (PET) images for functional brain mapping have been investigated. The scatter fraction and noise-equivalent count rate characteristics were measured for the ECAT 951/31R PET scanner operating in septa-extended two-dimensional (2-D) and septa-retracted three-dimensional (3-D) modes. The 3-D mode is shown to provide higher signal-to-noise images than the 2-D mode at specific activities less than 30 kBq/ml. To enable increased temporal resolution in dynamic 3-D PET activation studies, a parallel version of the 3-D reconstruction algorithm was developed. Implementation of the reprojection algorithm on an 88 processor i860 supercomputer resulted in a more than tenfold increase in reconstruction speed compared to a single i860 processor system. An investigation of the optimal duration for imaging brain activations was undertaken in 12 normal subjects using repeated H/sub 2//sup 15/O slow infusions and a visually presented lexical decision task. The significance of change in regional cerebral blood flow (CBF) was determined using statistical parametric maps for images acquired during stimulation, immediately after stimulation, and commencing 1 min after cessation of the stimulus. Regions of CBF change were detected in all three images. Dynamic 3-D, or four-dimensional (4-D), PET activation scanning is shown to be practical and likely to further improve the sensitivity of PET for detection of subtle regional CBF changes in functional brain mapping research.

Neuroscientists have constantly sought new methods of evaluating brain function, with progressive improvement in the last century in imaging brain structure and function. However, except for direct surgical stimulation, neuropsychiatrists can only infer causality between the signal obtained on an image and a behavior or disease. Transcranial magnetic stimulation (TMS) is a new, noninvasive technique for directly stimulating cortical neurons. It has been used to map attention, memory, movement, speech, and vision. Preliminary investigations have also used rapid-rate TMS to improve motor speed in Parkinson's disease and mood in depression. TMS is likely to be an important future neuropsychiatric tool.

Metabolic analysis using magnetic resonance spectroscopy may provide accurate noninvasive pathological diagnosis in brain tumors (pages 323–325).

A single-photon emission tomograph has been designed and built for regional studies of brain blood flow using 133Xe or 127Xe. The dynamic computer assisted tomograph (DCAT) features fast rotation of a square array of detectors enabling the collection of data in 5 sec, simultaneous recording

To obtain high quality computed tomographic (CT) images of specimens, the specimens must be submerged in water and immobilized. We describe a simple, effective technique for imaging brain specimens in various CT scanners. Anatomic sections that correspond exactly to the plane of the CT image may be obtained