Functional MRI Techniques Research Articles

Compressed sensing reconstruction improves sensitivity of variable density spiral fMRI

Functional MRI (fMRI) techniques that can provide excellent blood oxygen level dependent contrast, rapid whole brain imaging, and minimal spatial distortion are in demand. This study explored whether fMRI sensitivity can be improved through the use of compressed sensing (CS) reconstruction of variable density spiral fMRI. Three different CS-reconstructed 1-shot variable density spirals were explored (corresponding to 28%, 35%, and 46% under-sampling), and compared with conventional 1-shot and 2-shot Archimedean spirals acquired using matched echo time and volume repetition time. fMRI maps were reconstructed with or without CS MRI and sensitivity was compared using identically matched voxels. The results demonstrated that an l1 -norm based CS reconstruction only led to an increase in functional contrast when applied to 28% under-sampled data. A whole brain t-contrast map revealed that 2-shot uniformly sampled spiral and 28% under-sampled spiral data reconstructed with CS yield equivalent sensitivity, even with matched echo time and volume repetition time VD spiral exhibits a useful operating range, in the region of 25-30% under-sampling, for which CS reconstruction can be used to increase the sensitivity of fMRI to brain activity. Using CS, VD acquisitions achieve the same sensitivity as 2-shot Archimedean acquisitions, but require only a single shot.

MRI of ovarian masses

MRI provides exquisite views of the pelvic anatomy through its high spatial resolution and tissue contrast, and as such plays a key role in the work up of ovarian lesions, identifying features that distinguish benign and malignant lesions. In the case of primary tumors it enables local staging and detection of metastatic disease to help guide management options such as complex surgery or the consideration of neoadjuvant chemotherapy. Functional MRI techniques such as diffusion-weighted MRI (DW-MRI), dynamic contrast-enhanced MRI (DCE-MRI) and tumor-selective molecular imaging are currently being evaluated as possible predictive and prognostic biomarkers in the context of ovarian malignancy, and may play a larger role in routine clinical practice in the future. Herein we provide an overview of the conventional and advanced MRI techniques used to characterize ovarian masses and of the role that MR plays in the staging, treatment selection and follow up of patients with ovarian cancer.

Altered functional brain networks in Prader–Willi syndrome

Prader-Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating-related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting-state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low-frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting-state brain activity levels in patients compared with their sibling control group. We then applied a functional connectivity (FC) analysis to these regions of interest in order to characterize interactions among the brain regions. Our results demonstrated that patients with PWS showed decreased FC strength in the medial prefrontal cortex (MPFC)/inferior parietal lobe (IPL), MPFC/precuneus, IPL/precuneus and IPL/hippocampus in the default mode network; decreased FC strength in the pre-/postcentral gyri and dorsolateral prefrontal cortex (DLPFC)/orbitofrontal cortex (OFC) in the motor sensory network and prefrontal cortex network, respectively; and increased FC strength in the anterior cingulate cortex/insula, ventrolateral prefrontal cortex (VLPFC)/OFC and DLPFC/VLPFC in the core network and prefrontal cortex network, respectively. These findings indicate that there are FC alterations among the brain regions implicated in eating as well as rewarding, even during the resting state, which may provide further evidence supporting the use of PWS as a model to study obesity and to provide information on potential neural targets for the medical treatment of overeating.

Functional magnetic resonance imaging with an ultrashort echo time

The purpose of the authors study was to investigate a functional MRI (fMRI) technique with an ultrashort echo-time (UTE) sequence. An UTE-based fMRI technique was applied to 17 young healthy volunteers during visual stimulations on a 3T MRI system. In addition, a blood oxygen level-dependent (BOLD) fMRI image was also obtained to compare functional changes in the brain. The one-sample t-test was performed to investigate increased or decreased signals during baseline and stimulation conditions for all subjects. Furthermore, regions-of-interest were placed by selecting one of the peak activated voxels from the UTE-based and BOLD data to investigate the level of signal changes on the time-course. During the visual activation period, the decreased signals were shown in the visual cortex for the UTE-based method, while both increased and decreased signals were found in the cortex for the BOLD method. The averaged signal changes for the UTE-based data were -0.48 ± 0.37% in the left lingual gyrus, while the changes on the BOLD data were 1.71 ± 0.87% in the right lingual gyrus. The UTE-based fMRI technique can detect the neuronal activity corresponding to neuronal function. The UTE-based method should be able to improve spatial localization and has much lower sensitivity to field inhomogeneities. Therefore, UTE-based fMRI can be useful to the neurosciences and clinical populations.

Imaging structural and functional brain networks in temporal lobe epilepsy

Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy.

Late-life depression, mild cognitive impairment and hippocampal functional network architecture.

Late-life depression (LLD) and amnestic mild cognitive impairment (aMCI) are associated with medial temporal lobe structural abnormalities. However, the hippocampal functional connectivity (HFC) similarities and differences related to these syndromes when they occur alone or coexist are unclear. Resting-state functional connectivity MRI (R-fMRI) technique was used to measure left and right HFC in 72 elderly participants (LLD [n = 18], aMCI [n = 17], LLD with comorbid aMCI [n = 12], and healthy controls [n = 25]). The main and interactive relationships of LLD and aMCI on the HFC networks were determined, after controlling for age, gender, education and gray matter volumes. The effects of depressive symptoms and episodic memory deficits on the hippocampal functional connections also were assessed. While increased and decreased left and right HFC with several cortical and subcortical structures involved in mood regulation were related to LLD, aMCI was associated with globally diminished connectivity. Significant LLD–aMCI interactions on the right HFC networks were seen in the brain regions critical for emotion processing and higher-order cognitive functions. In the interactive brain regions, LLD and aMCI were associated with diminished hippocampal functional connections, whereas the comorbid group demonstrated enhanced connectivity. Main and interactive effects of depressive symptoms and episodic memory performance were also associated with bilateral HFC network abnormalities. In conclusion, these findings indicate that discrete hippocampal functional network abnormalities are associated with LLD and aMCI when they occur alone. However, when these conditions coexist, more pronounced vulnerabilities of the hippocampal networks occur, which may be a marker of disease severity and impending cognitive decline. By utilizing R-fMRI technique, this study provides novel insights into the neural mechanisms underlying LLD and aMCI in the functional network level.

Ultra high spatial and temporal resolution breast imaging at 7T

There is a need to obtain higher specificity in the detection of breast lesions using MRI. To address this need, Dynamic Contrast-Enhanced (DCE) MRI has been combined with other structural and functional MRI techniques. Unfortunately, owing to time constraints structural images at ultra-high spatial resolution can generally not be obtained during contrast uptake, whereas the relatively low spatial resolution of functional imaging (e.g. diffusion and perfusion) limits the detection of small lesions. To be able to increase spatial as well as temporal resolution simultaneously, the sensitivity of MR detection needs to increase as well as the ability to effectively accelerate the acquisition. The required gain in signal-to-noise ratio (SNR) can be obtained at 7T, whereas acceleration can be obtained with high-density receiver coil arrays. In this case, morphological imaging can be merged with DCE-MRI, and other functional techniques can be obtained at higher spatial resolution, and with less distortion [e.g. Diffusion Weighted Imaging (DWI)]. To test the feasibility of this concept, we developed a unilateral breast coil for 7T. It comprises a volume optimized dual-channel transmit coil combined with a 30-channel receive array coil. The high density of small coil elements enabled efficient acceleration in any direction to acquire ultra high spatial resolution MRI of close to 0.6 mm isotropic detail within a temporal resolution of 69 s, high spatial resolution MRI of 1.5 mm isotropic within an ultra high temporal resolution of 6.7 s and low distortion DWI at 7T, all validated in phantoms, healthy volunteers and a patient with a lesion in the right breast classified as Breast Imaging Reporting and Data System (BI-RADS) IV.

Functional MRI as a Biomarker for Evaluation and Prediction of Effectiveness of Migraine Prophylaxis

Migraine is a neurological disorder characterized by episodic head pain and visual cortical phenomena. The pathogenesis of migraine is unknown and remains to be determined. Bright light, flickering light and certain visual patterns can trigger a migraine attack, and visual cortical hyperexcitability has been hypothesized to be responsible. Interictally, the brain of migraineurs functions normally under general conditions but abnormally only under some specific conditions, such as the observation of stressful visual patterns, suggesting studying the brain function could provide insights in migraine pathophysiology. The functional MRI technique is unique in probing specific cortical area activation under various stimulation conditions and studying the abnormal cortical activation associated with functional disorders in migraine. In this perspective, we discuss how a novel functional MRI technique can be used to identify those migraineurs suffering visual cortical hyperexcitability, and its potential as a biomarker to evaluate and possibly predict effectiveness of migraine-preventive treatments.

WE-E-BRA-02: Optimization of Functional MRI Techniques for Assessment of Tumor and Normal Tissue Response to RT.

1. Understand new MRI technologies that are relevant to radiation treatment assessment; 2. Understand the influence of imaging parameters on image quality and contrast; 3. Understand image processing techniques for derived quantitative parameters; 4. Understand clinical applications and limitations. Author's work is supported in part by NIH P01 CA59827, NCI RO1 CA132834, and RO1 NS064973. 3959.

From neuroimaging to clinical setting: what have we learned from migraine pain?

In the last 15 years, the neuroimaging of patients suffering from migraine with or without aura has improved our understanding of the mechanisms underlying the pathophysiology of the disease. A great number of studies based on modern imaging techniques, such as structural imaging and functional imaging emphasize that in migraine patients suffering from repetitive pain attacks, both significant abnormalities of function and diffuse structural changes of brain white and gray matter become striking features of the disease. The hypothesis that migraine pain is due to a global brain disorder with substantial brainstem involvement leading to secondary blood flow changes in the posterior circulation is reinforced by several elegant studies. Clinical application of functional imaging findings in migraine is yet to be considered, since the specificity of some results has to be determined. Nevertheless, functional MRI techniques have a vast potential for exploring the pathophysiology of pain in migraine patients.

Brain Response to the Luminal Nutrient Stimulation

Nutrient signals called postingestive effects are thought to be the sixth sensory signals (gut feeling). They modulate motivation to eat and subsequent food preference. Although the other five senses are well-characterized, there are still a lot of mysteries in the processing of luminal nutrient information in the brain. Development of functional MRI (fMRI) technique during the past 10 years enabled researchers to investigate brain function for the detection, perception, and processing of chemosensory information in human beings. We developed an awake rat fMRI technique to investigate whole brain function for the detection of ingested nutrients. Here we will review a recent study of luminal nutrient information in humans and in rodents.

Role of New Functional MRI Techniques in the Diagnosis, Staging, and Followup of Gynecological Cancer: Comparison with PET-CT

Recent developments in diagnostic imaging techniques have magnified the role and potential of both MRI and PET-CT in female pelvic imaging. This article reviews the techniques and clinical applications of new functional MRI (fMRI) including diffusion-weighted MRI (DWI), dynamic contrast-enhanced (DCE)-MRI, comparing with PET-CT. These new emerging provide not only anatomic but also functional imaging, allowing detection of small volumes of active tumor at diagnosis and early disease relapse, which may not result in detectable morphological changes at conventional imaging. This information is useful in distinguishing between recurrent/residual tumor and post-treatment changes and assessing treatment response, with a clear impact on patient management. Both PET-CT and now fMRI have proved to be very valuable tools for evaluation of gynecologic tumors. Most papers try to compare these techniques, but in our experience both are complementary in management of these patients. Meanwhile PET-CT is superior in diagnosis of ganglionar disease; fMRI presents higher accuracy in local preoperative staging. Both techniques can be used as biomarkers of tumor response and present high accuracy in diagnosis of local recurrence and peritoneal dissemination, with complementary roles depending on histological type, anatomic location and tumoral volume.

OT2-03-06: ACRIN 6698 MR Imaging Biomarkers for Assessment of Breast Cancer Response to Neoadjuvant Chemotherapy: A Sub-Study of the I-SPY 2 TRIAL (Investigation of Serial Studies To Predict Your Therapeutic Response with Imaging And moLecular Analysis).

Abstract Background Functional MRI techniques may be utilized for characterizing breast tumors and measuring response to neoadjuvant chemotherapy (NAC). Dynamic contrast enhanced (DCE) MRI is the most common functional breast MRI technique. Fitting DCE MRI data to an appropriate pharmacokinetic model allows noninvasive, in vivo measurement of physiological parameters related to tissue perfusion, microvascular permeability, and extracellular/extravascular volume fraction. Diffusion weighted imaging (DWI) MRI is an alternative technique that measures the mobility of water molecules in vivo and is sensitive to tissue characteristics such as cell density, membrane permeability, and microstructure. DWI provides complementary information to DCE MRI about tumor biology and has shown promise for early prediction of response. The master ISPY2 multi-center study is a process targeting the rapid, focused clinical development of paired oncologic therapies and biomarkers. Its framework is an adaptive phase II clinical trial design in the neoadjuvant setting for women with locally advanced breast cancer. As a sub-study, ACRIN 6698 will combine both DCE and DWI MRI data to generate novel imaging biomarkers that correlate with treatment response. The two studies will provide a rich data set that can be used to elucidate molecular pathways and tumor responses to novel investigational drugs with standard chemotherapy. Trial design: ACRIN 6698 will perform advanced DCE and DWI MR imaging as part of the I-SPY TRIAL. The ISPY 2 adaptive therapy design will use different tumor biomarker assays to identify patients with high risk of recurrence. Patients will receive NAC doublet chemotherapy and trastuzumab (if Her2+). Patients will be randomized and stratified into different arms receiving investigational agents of different drug classes. ACRIN 6698 patients will receive four advanced MRI exams (both DCE and DWI) at baseline, early therapy, mid therapy and prior to surgery. Specific aims: The primary aim will determine if the % change in tumor apparent diffusion coefficient (ADC) measured on DWI from baseline to early treatment timepoint is predictive of pathologic complete response (pCR). The secondary aim will determine if the combined measurement of percentage change in tumor ADC on DWI, and percentage change in tumor volume and peak signal enhancement ratio (SER) on DCE MRI is predictive of pCR. Statistical methods: Receiver operating characteristic (ROC) curve and corresponding area under the ROC curves (AUC) for the individual marker, % change in tumor ADC, and % change in tumor volume and peak SER, will be estimated. Linear score of the 3 markers will be derived by fitting the multivariate logistic regression model, where the outcome is a binary variable for pCR and the predictors are the 3 measurements. The ROC curve for the derived linear score will be constructed and its AUC value will be estimated. Target accrual: ACRIN 6698 is open to ISPY 2 sites. The target accrual is 200 of ISPY 2's planned enrollment of 800 participants. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-03-06.

Relative Function: Nuclear Brain Imaging in United States Courts

Neuropsychological testing—medical imaging of the brain structure and function—allows the expert to inform the court on the brain structure and function of the forensic examinee. Supported by extensive clinical use, neuropsychological testing and structural imaging in the form of computerized tomography and structural magnetic resonance imaging have achieved general acceptance in court. However, functional imaging such as functional MRI and nuclear medicine techniques, such as positron emission tomography (PET), have faced more admissibility challenges. While functional imaging is becoming an increasingly important tool in assessing neuropsychiatric illness, we surmise that evidentiary challenges are largely related to the phase of trial in which the nuclear study is offered as evidence. This article will review the basic science of functional nuclear imaging including PET and single photon emission computed tomography. We will then review cases where admissibility of these techniques has been challenged and consider whether and how nuclear brain imaging can influence the outcome of the trial.

Imaging cervical cancer

There has been considerable progress in the imaging of cervical cancer over the last 5 years. In countries with access to cross-sectional imaging resources, technical advances have enabled a range of imaging techniques to become increasingly employed and established in the detection, staging and treatment planning of cervical cancer and for identifying disease recurrence. This review highlights these developments and summarizes recent significant articles. Functional imaging techniques provide information on tumour biology by probing characteristics of tumour vascularity, cellularity and metabolism which critically contribute to decision making and stratification for management options. Particularly, functional MRI techniques have improved accuracy of disease staging and detection of recurrence. PET-computed tomography is useful in lymph node staging and targeted radiotracers are increasingly exploited as potential biomarkers of treatment response. Improvements in hardware, software and contrast agents are revolutionizing the role of imaging in cervical cancer. Once standardized and validated, the techniques should enable individualized patient treatment and optimization of outcome.

Hypothyroidism and mood disorders: integrating novel insights from brain imaging techniques

Thyroid hormones play a critical role in brain development but also in the adult human brain by modulating metabolic activity. Hypothyroid states are associated with both functional and structural brain alterations also seen in patients with major depression. Recent animal experimental and preclinical data indicate subtle changes in myelination, microvascular density, local neurogenesis, and functional networks. The translational validity of such studies is obviously limited. Clinical evidence for neurobiological correlates of different stages and severities of hypothyroidism and effects of pharmacological intervention is lacking but may be achieved using advanced imaging techniques, e.g. functional and quantitative MRI techniques applied to patients with hypothyroidism before and after hormone replacement therapy.

Quantitative pharmacologic MRI in mice

Pharmacologic MRI (phMRI) uses functional MRI techniques to provide a noninvasive in vivo measurement of the hemodynamic effects of drugs. The cerebral blood volume change (ΔCBV) serves as a surrogate for neuronal activity via neurovascular coupling mechanisms. By assessing the location and time course of brain activity in mouse mutant studies, phMRI can provide valuable insights into how different behavioral phenotypes are expressed in deferring brain activity response to drug challenge. In this report, we evaluate the utility of three different intravascular ultrasmall superparamagnetic iron oxide (USPIO) contrast agents for phMRI using a gradient-echo technique, with temporal resolution of one min at high magnetic field. The tissue half-life of the USPIOs was studied using a nonlinear detrending model. The three USPIOs are candidates for CBV weighted phMRI experiments, with r(2)/r(1) ratios ≥ 20 and apparent half-lives ≥ 1.5 h at the described doses. An echo-time of about 10 ms or longer results in a functional contrast to noise ratio (fCNR) > 75 after USPIO injection, with negligible decrease between 1.5-2 h. phMRI experiments were conducted at 7 T using cocaine as a psychotropic substance and acetazolamide, a global vasodilator, as a positive control. Cocaine acts as a dopamine-serotonin-norepinephrine reuptake inhibitor, increasing extracellular concentrations of these neurotransmitters, and thus increasing dopaminergic, serotonergic and noradrenergic neurotransmission. phMRI results showed that CBV was reduced in the normal mouse brain after cocaine challenge, with the largest effects in the nucleus accumbens, whereas after acetazolamide, blood volume was increased in both cerebral and extracerebral tissue.

Potential for Transcutaneous Vagus Nerve Stimulation in Pain Management

ISSN 1758-1869 10.2217/PMT.11.27 © 2011 Future Medicine Ltd Pain Manage. (2011) 1(4), 287–289 Currently available therapeutic interven‐ tions for chronic pain disorders are less than ideal. For this reason, new interven‐ tion strategies complementing existing therapeutical approaches are urgently needed. In this context, neurostimulation methods may represent potential success‐ ful tools for managing clinical pain syn‐ dromes. Besides transcranial magnetic stimulation, vagus nerve stimulation (VNS) may open a window for a new pain‐relieving treatment method. Interestingly, the anatomy and physio‐ logy of the vagus nerve (X cranial) is com‐ plex and until recently not well character‐ ized. The vagus nerve was traditionally considered as a purely parasympathetic efferent nerve. However, recent work dem‐ onstrates that approximately 80% of the nerve fibers in the cervical nerve are affer‐ ent fibers [1]. These afferent sensory fibers project via the nucleus tractus solitarius to a variety of distinct brain areas, thereby rep‐ resenting an avenue for providing informa‐ tion into the CNS [2]. In detail, the nucleus tractus solitarius relays information to the parabrachial nucleus, the cerebellum, the periaqueductal gray and via ascending secondary projections to limbic areas such as the amygdalae as well as to paralimbic and cortical regions. This anatomically grounded bottom‐up way of stimulation led to the successful introduction of VNS as a neurostimulation modality affecting the limbic system and thereby associated neuropsychiatric diseases such as epilepsy and treatment‐resistant depression. Based on this potential to reach brain areas such as the periaqueductal gray, thalamic nuclei or limbic areas, which are closely involved in pain processing, it was hypothesized that VNS may bear antinoci‐ ceptive qualities [3]. In fact, neuroimaging studies using SPECT, PET and functional MRI techniques provided additional evi‐ dence that VNS changes cerebral activity in pain‐processing cortical and subcorti‐ cal regions like the dorsal‐rostral medulla, bilateral thalamus, right postcentral gyrus or the anterior cingulate cortex [4]. For this reason, most arguments favor a potential central mode of VNS antinociception, complemented by peripheral mechanisms such as a modulation of primary afferent nociceptors [5]. In this context, animal studies have demonstrated an inhibitory effect of VNS on the electric response of spinal

Resting-state brain networks: literature review and clinical applications

This review focuses on resting-state functional connectivity, a functional MRI technique which allows the study of spontaneous brain activity generated under resting conditions. This approach is useful to explore the brain's functional organization and to examine if it is altered in neurological or psychiatric diseases. Resting-state functional connectivity has revealed a number of networks which are consistently found in healthy subjects and represent specific patterns of synchronous activity. In this review, we examine the behavioral, physiological and neurological evidences relevant to this coherent brain activity and, in particular, to each network. The investigation of functional connectivity appears promising from a clinical perspective, considering the amount of evidence regarding the importance of spontaneous activity and that resting-state paradigms are inherently simple to implement. We also discuss some examples of existing clinical applications, such as in Alzheimer's disease, and emerging possibilities such as in pre-operative mapping and disorders of consciousness.

Attention‐related networks in Alzheimer's disease: A resting functional MRI study

In addition to memory deficits, attentional impairment is a common manifestation of Alzheimer's disease (AD). The present study examines the abnormalities of attention-related functional networks in AD using resting functional MRI (fMRI) technique and evaluates the sensitivity and specificity of these networks as potential biomarkers compared with the default mode network (DMN). Group independent component analysis (Group ICA) was applied to fMRI data from 15 AD patients and 16 normal healthy elderly controls (NC) to derive the dorsal attention network (DAN) and the ventral attention network (VAN) which are respectively responsible for the endogenous attention orienting ("top-down") process and the exogenous attention re-orienting ("bottom-up") process. Receiver operating characteristic (ROC) curve analysis was performed for activity in core regions within each of these networks. Functional connectivity analysis revealed disrupted DAN and preserved (less impaired) VAN in AD patients compared with NC, which might indicate impairment of a "top-down" and intact "bottom-up" attentional processing mechanisms in AD. ROC curve analysis suggested that activity in the left intraparietal sulcus and left frontal eye field from DAN as well as the posterior cingulate cortex from the DMN could serve as sensitive and specific biomarkers distinguishing AD from NC.