Functional Imaging Modalities Research Articles

Hemodynamic response to sensory stimulation in mice: Comparison between functional ultrasound and optoacoustic imaging

Intense efforts are underway to develop functional imaging modalities for capturing brain activity at the whole organ scale with high spatial and temporal resolution. Functional optoacoustic (fOA) imaging is emerging as a new tool to monitor multiple hemodynamic parameters across the mouse brain, but its sound validation against other neuroimaging modalities is often lacking. Here we investigate mouse brain responses to peripheral sensory stimulation using both fOA and functional ultrasound (fUS) imaging. The two modalities operate under similar spatio-temporal resolution regime, with a potential to provide synergistic and complementary hemodynamic readouts. Specific contralateral activation was observed with sub-millimeter spatial resolution with both methods. Sensitivity to hemodynamic activity was found to be on comparable levels, with the strongest responses obtained in the oxygenated hemoglobin channel of fOA. While the techniques attained highly correlated hemodynamic responses, the differential fOA readings of oxygenated and deoxygenated haemoglobin provided complementary information to the blood flow contrast of fUS. The multi-modal approach may thus emerge as a powerful tool providing new insights into brain function, complementing our current knowledge generated with well-established neuroimaging methods.

Deep learning in structural and functional lung image analysis.

The recent resurgence of deep learning (DL) has dramatically influenced the medical imaging field. Medical image analysis applications have been at the forefront of DL research efforts applied to multiple diseases and organs, including those of the lungs. The aims of this review are twofold: (i) to briefly overview DL theory as it relates to lung image analysis; (ii) to systematically review the DL research literature relating to the lung image analysis applications of segmentation, reconstruction, registration and synthesis. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. 479 studies were initially identified from the literature search with 82 studies meeting the eligibility criteria. Segmentation was the most common lung image analysis DL application (65.9% of papers reviewed). DL has shown impressive results when applied to segmentation of the whole lung and other pulmonary structures. DL has also shown great potential for applications in image registration, reconstruction and synthesis. However, the majority of published studies have been limited to structural lung imaging with only 12.9% of reviewed studies employing functional lung imaging modalities, thus highlighting significant opportunities for further research in this field. Although the field of DL in lung image analysis is rapidly expanding, concerns over inconsistent validation and evaluation strategies, intersite generalisability, transparency of methodological detail and interpretability need to be addressed before widespread adoption in clinical lung imaging workflow.

Hybrid imaging of complicating osteomyelitis in the peripheral skeleton.

Diagnosing complicating osteomyelitis (COM) is clinically challenging. Laboratory tests are of limited utility, and other than isolation of the offending organism, diagnostic imaging tests are of paramount importance. Nuclear Medicine techniques play an important role in noninvasive evaluation of osteomyelitis, using both single-photon emission tomography (SPECT) and positron emission tomography (PET) radiopharmaceuticals. It is well-known that those conventional imaging modalities are not performing well in the distinction between soft-tissue and deep bone infection due to the lack of anatomical information. These difficulties have been overcome, to a great extent, with the introduction of in-line SPECT-CT and PET-CT systems which have revolutionized the field of diagnostic medical imaging. Hybrid imaging is especially useful in sites of suspected COM with underlying structural bone alterations. The first clinical studies with these integrated hybrid machines in the field of COM, including metallic implants imaging, are highly promising. In summary, WBC/AGA SPECT-CT and FDG-PET-CT seem to be the most accurate hybrid imaging modality for COM of the peripheral bone. However, there are still false positives, especially in aseptic tibial nonunions and/or metallic implants, as well as in the immediate postoperative setting. Furthermore, there is a lack of well-designed large multicentre prospective studies. Hopefully, in the future, the complementary use of morphological and functional hybrid imaging modalities may overcome some of the challenges faced in the assessment of COM.

Simulation Study of a Frame-Based Motion Correction Algorithm for Positron Emission Imaging.

Positron emission tomography (PET) is a functional non-invasive imaging modality that uses radioactive substances (radiotracers) to measure changes in metabolic processes. Advances in scanner technology and data acquisition in the last decade have led to the development of more sophisticated PET devices with good spatial resolution (1–3 mm of full width at half maximum (FWHM)). However, there are involuntary motions produced by the patient inside the scanner that lead to image degradation and potentially to a misdiagnosis. The adverse effect of the motion in the reconstructed image increases as the spatial resolution of the current scanners continues improving. In order to correct this effect, motion correction techniques are becoming increasingly popular and further studied. This work presents a simulation study of an image motion correction using a frame-based algorithm. The method is able to cut the acquired data from the scanner in frames, taking into account the size of the object of study. This approach allows working with low statistical information without losing image quality. The frames are later registered using spatio-temporal registration developed in a multi-level way. To validate these results, several performance tests are applied to a set of simulated moving phantoms. The results obtained show that the method minimizes the intra-frame motion, improves the signal intensity over the background in comparison with other literature methods, produces excellent values of similarity with the ground-truth (static) image and is able to find a limit in the patient-injected dose when some prior knowledge of the lesion is present.

Neuroimaging of depression with diffuse optical tomography during repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for depression; however, its potential has likely been hindered due to non-optimized targeting, unclear ideal stimulation parameters, and lack of information regarding how the brain is physiologically responding during and after stimulation. While neuroimaging is ideal for obtaining such critical information, existing modalities have been limited due to poor resolutions, along with significant noise interference from the electromagnetic spectrum. In this study, we used a novel diffuse optical tomography (DOT) device in order to advance our understanding of the neurophysiological effects of rTMS in depression. Healthy and depressed subjects aged 18–70 were recruited. Treatment parameters were standardized with targeting of the left dorsolateral prefrontal cortex with a magnetic field intensity of 100% of motor threshold, pulse frequency of 10 per second, a 4 s stimulation time and a 26 s rest time. DOT imaging was simultaneously acquired from the contralateral dorsolateral prefrontal cortex. Six healthy and seven depressed subjects were included for final analysis. Hemoglobin changes and volumetric three-dimensional activation patterns were successfully captured. Depressed subjects were observed to have a delayed and less robust response to rTMS with a decreased volume of activation compared to healthy subjects. In this first-in-human study, we demonstrated the ability of DOT to safely and reliably capture and compare cortical response patterns to rTMS in depressed and healthy subjects. We introduced this emerging optical functional imaging modality as a novel approach to investigating targeting, new treatment parameters, and physiological effects of rTMS in depression.

Phenotype discovery from population brain imaging.

Neuroimaging allows for the non-invasive study of the brain in rich detail. Data-driven discovery of patterns of population variability in the brain has the potential to be extremely valuable for early disease diagnosis and understanding the brain. The resulting patterns can be used as imaging-derived phenotypes (IDPs), and may complement existing expert-curated IDPs. However, population datasets, comprising many different structural and functional imaging modalities from thousands of subjects, provide a computational challenge not previously addressed. Here, for the first time, a multimodal independent component analysis approach is presented that is scalable for data fusion of voxel-level neuroimaging data in the full UK Biobank (UKB) dataset, that will soon reach 100,000 imaged subjects. This new computational approach can estimate modes of population variability that enhance the ability to predict thousands of phenotypic and behavioural variables using data from UKB and the Human Connectome Project. A high-dimensional decomposition achieved improved predictive power compared with widely-used analysis strategies, single-modality decompositions and existing IDPs. In UKB data (14,503 subjects with 47 different data modalities), many interpretable associations with non-imaging phenotypes were identified, including multimodal spatial maps related to fluid intelligence, handedness and disease, in some cases where IDP-based approaches failed.

Multidimensional Diffusion Magnetic Resonance Imaging for Characterization of Tissue Microstructure in Breast Cancer Patients: A Prospective Pilot Study.

Simple SummaryIn this prospective pilot study, we investigated the potential of clinical multidimensional diffusion magnetic resonance imaging (MDD MRI) for the microstructural characterization of breast cancers and normal fibroglandular breast tissue. The method relies on advanced gradient waveforms to encode the signal with information about cell densities, shapes, and orientations, and to quantify tissue composition as a probability distribution of diffusion tensors in a space with dimensions analogous to those on a cellular level. Sixteen patients with breast cancer underwent MDD MRI within a clinically feasible scan time of approximately 4 min, providing voxel-resolved distributions and parameter maps with microstructural information that is not accessible with conventional methods.Diffusion-weighted imaging is a non-invasive functional imaging modality for breast tumor characterization through apparent diffusion coefficients. Yet, it has so far been unable to intuitively inform on tissue microstructure. In this IRB-approved prospective study, we applied novel multidimensional diffusion (MDD) encoding across 16 patients with suspected breast cancer to evaluate its potential for tissue characterization in the clinical setting. Data acquired via custom MDD sequences was processed using an algorithm estimating non-parametric diffusion tensor distributions. The statistical descriptors of these distributions allow us to quantify tissue composition in terms of metrics informing on cell densities, shapes, and orientations. Additionally, signal fractions from specific cell types, such as elongated cells (bin1), isotropic cells (bin2), and free water (bin3), were teased apart. Histogram analysis in cancers and healthy breast tissue showed that cancers exhibited lower mean values of “size” (1.43 ± 0.54 × 10−3 mm2/s) and higher mean values of “shape” (0.47 ± 0.15) corresponding to bin1, while FGT (fibroglandular breast tissue) presented higher mean values of “size” (2.33 ± 0.22 × 10−3 mm2/s) and lower mean values of “shape” (0.27 ± 0.11) corresponding to bin3 (p < 0.001). Invasive carcinomas showed significant differences in mean signal fractions from bin1 (0.64 ± 0.13 vs. 0.4 ± 0.25) and bin3 (0.18 ± 0.08 vs. 0.42 ± 0.21) compared to ductal carcinomas in situ (DCIS) and invasive carcinomas with associated DCIS (p = 0.03). MDD enabled qualitative and quantitative evaluation of the composition of breast cancers and healthy glands.

Functional and structural brain connectivity in congenital deafness.

Several studies have been carried out to verify neural plasticity and the language process in deaf individuals. However, further investigations regarding the intrinsic brain organization on functional and structural neural networks derived from congenital deafness are still an open question. The objective of this study was to investigate the main differences in brain organization manifested in congenitally deaf individuals, concerning the resting-state functional patterns, and white matter structuring. Functional and diffusion magnetic resonance imaging modalities were acquired from 18 congenitally deaf individuals and 18 age-sex-matched hearing controls. Compared to the hearing group, the deaf individuals presented higher functional connectivity among the posterior cingulate cortex node of the default mode network with visual and motor networks, lower functional connectivity between salience networks, language networks, and prominence of functional connectivity changes in the right hemisphere, mostly in the frontoparietal and temporal lobes. In terms of structural connectivity, we found changes mainly in the occipital and parietal lobes, involving both classical sign language support regions as well as concentrated networks for focus activity, attention, and cognitive filtering. Our findings demonstrated that the congenital deaf individuals who learned sign language developed significant brain functional and structural reorganization, which provides prominent support for large-scale brain networks associated with attention decision-making, environmental monitoring based on the movement of objects, and on the motor and visual controls.

Multiparametric magnetic resonance imaging and positron emission tomography findings in neurodegenerative diseases: Current status and future directions.

Neurodegenerative diseases (NDDs) are characterized by progressive neuronal loss, leading to dementia and movement disorders. NDDs broadly include Alzheimer's disease, frontotemporal lobar degeneration, parkinsonian syndromes, and prion diseases. There is an ever-increasing prevalence of mild cognitive impairment and dementia, with an accompanying immense economic impact, prompting efforts aimed at early identification and effective interventions. Neuroimaging is an essential tool for the early diagnosis of NDDs in both clinical and research settings. Structural, functional, and metabolic imaging modalities, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are widely available. They show encouraging results for diagnosis, monitoring, and treatment response evaluation. The current review focuses on the complementary role of various imaging modalities in relation to NDDs, the qualitative and quantitative utility of newer MRI techniques, novel radiopharmaceuticals, and integrated PET/MRI in the setting of NDDs.

Development of a mechatronic guidance system for targeted ultrasound-guided biopsy under high-resolution positron emission mammography localization.

Image-guided needle biopsy of small, detectable lesions is crucial for early-stage diagnosis, treatment planning, and management of breast cancer. High-resolution positron emission mammography (PEM) is a dedicated functional imaging modality that can detect breast cancer independent of breast tissue density, but anatomical context and real-time needle visualization are not yet available to guide biopsy. We propose a mechatronic guidance system integrating an ultrasound (US)-guided core-needle biopsy (CNB) with high-resolution PEM localization to improve the spatial sampling of breast lesions. This paper presents the benchtop testing and phantom studies to evaluate the accuracy of the system and its constituent components for targeted PEM-US-guided biopsy under simulated high-resolution PEM localization. A mechatronic guidance system was developed to operate with the Radialis PEM system and a conventional US system. The system includes a user-operated guidance arm and end-effector biopsy device, integrating a US transducer and CNB gun, with its needle focused on a remote center of motion (RCM). Custom software modules were developed to track, display, and guide the end-effector biopsy device. Registration of the mechatronic guidance system to a simulated PEM detector plate was performed using a landmark-based method. Testing was performed with fiducials positioned in the peripheral and central regions of the simulated detector plate and registration error was quantified. Breast phantom experiments were performed under ideal detection and localization to evaluate for bias in the end-effector biopsy device. The accuracy of the complete mechatronic guidance system to perform targeted breast biopsy was assessed using breast phantoms with simulated lesions. Three-dimensional positioning error was quantified, and principal component analysis assessed for directional trends in 3D space within 95% prediction intervals. Targeted breast biopsies with test phantoms were performed and an overall in-plane needle targeting error was quantified. The mean registration errors were 0.63mm (N=44) and 0.73mm (N=72) in the peripheral and central regions of the simulated PEM detector plate, respectively. A 3D 95% prediction ellipsoid shows an error volume <2.0mm in diameter, centered on the mean registration error. Under ideal detection and localization, targets <1.0mm in diameter can be sampled with 95% confidence. The complete mechatronic guidance system was able to successfully spatially sample simulated breast lesions, 4mm and 6mm in diameter and height (N=20) in known 3D positions in the PEM image coordinate space. The 3D positioning error was 0.85mm (N=20) with 0.64mm in-plane and 0.44mm cross-plane component errors. Targeted breast biopsies resulted in a mean in-plane needle targeting error of 1.08mm (N=15) allowing for targets 1.32mm in radius to be sampled with 95% confidence. We demonstrated the utility of our mechatronic guidance system for targeted breast biopsy under high-resolution PEM localization. Breast phantom studies showed the ability to accurately guide, position, and target breast lesions with the accuracy to spatially sample targets <3.0mm in diameter with 95% confidence. Future work will integrate the developed system with the Radialis PEM system toward combined PEM-US-guided breast biopsy.

Diffusion weighted imaging to predict nodal status in breast cancer: A systematic review and meta-analysis.

Diffusion weighted imaging is a functional imaging modality based upon Brownian water movement in tissues.1-3 This movement can be quantified by apparent diffusion coefficient (ADC). According to the literature, apparent diffusion coefficient (ADC) inversely correlates with histopathological features.1, 2 It was identified that benign breast lesions have significant higher ADC values compared to breast cancer (BC).5 Nodal status is one of the most important prognosis parameters in BC, which is assessed by axillary lymph node dissection.6 Our purpose was to systematically review the published literature regarding ADC values of BC in accordance with nodal status and the ADC values of axillary lymph nodes and perform a meta-analysis to establish, whether ADC values can reliably predict nodal status in BC. The literature was searched for suitable papers investigating the associations between ADC values and nodal status in BC. The meta-analysis was performed as previously described.5 The primary end point of the systematic review was association between nodal status of BC and ADC values of the primary tumor and axillary LN. In total, 23 studies were suitable for the analysis and were included into the present study. The acquired 23 studies comprised overall 1669 BC and 1423 LN. In total, 1025 nodal negative and 548 nodal positive BC were included into the analysis. The mean ADC of the primary tumor of the nodal positive BC was 0.89 × 10− 3 mm2/s [95% CI 0.84–0.94, I2 = 91%], and 0.96 × 10− 3 mm2/s [95% CI 0.91–1.01, I2 = 92%] of the nodal negative BC (Figure 1). In total, 876 benign and 547 malignant LN were included into the analysis. The mean ADC value of the malignant axillary LN was 0.90 × 10− 3 mm2/s [95% CI 0.80–1.01, I2 = 98%] and 1.17 × 10− 3 mm2/s [95% CI 1.02–1.32, I2 = 99%] of the benign LN (Figure 2). Three studies reported data regarding ADC values and LN size in large and short axis with overall 57 lymph nodes. Spearman's correlation coefficient for the large axis was r = −0.143, p = 0.29 and for the short axis was r = 0.024, p = 0.86. The present analysis showed that ADC values of the axillary LN are lower in malignant LN compared to benign LN and might aid in clinical decision-making. Similar findings were identified of the ADC values of primary tumors to predict nodal status in BC. Thus, the present analysis based upon a large sample size corroborates the results of previous single-center studies. Nodal status is one of the most important prognosis factors in BC, which leads to a worse outcome in patients with positive axillary lymph nodes compared to nodal negative patients.6 A precise definition of the status of axillary LN in BC patients is also important to select treatment modality or surgical method. Axillary LN dissection is the reference standard for evaluating nodal involvement. Several imaging modalities were used to predict LN status non-invasively. So, ultrasound was deemed to be unreliable.7 The cost expensive modality with radiation exposure, namely PET-CT, achieved only a pooled sensitivity of 56% in a recent meta-analysis, whereas morphological MRI achieved a sensitivity of 55% only.7 However, both modalities reached a high specificity of 91% and 86%, respectively. Yet, there is definite need for a better diagnostic modality to predict nodal status in BC. The present analysis tried to emphasize that DWI and ADC values might be able to fill this diagnostic gap with measurement of the primary tumor itself as well as with the measurement of the lymph nodes. Interestingly, ADC values are independent of the lymph node size, which is most often used in clinical routine as a sign for malignancy. The present analysis can state that ADC values are not correlated with the short and long axis size of the lymph nodes. Presumably, a primary tumor with nodal involvement has a more aggressive tumor biology with distinctive microstructure, which can be assessed by ADC values. Moreover, there is clear evidence that ADC values can aid in the discrimination between benign and malignant tumors, which was shown in a recent meta-analysis.5 So, the present analysis can harmonize the published results that ADC values of the primary tumor as well as of the axillary lymph nodes can aid to predict nodal status in BC. As a limitation to address, the meta-analysis is based upon published results in the literature. There might be a certain publication bias because there is a trend to report positive or significant results. In conclusion, ADC values of axillary LN and of primary tumors may aid in predict nodal status of BC in clinical routine. These results are based upon a large patient sample and can be considered representative.

Flash Scanning Volumetric Optoacoustic Tomography for High Resolution Whole‐Body Tracking of Nanoagent Kinetics and Biodistribution

AbstractTracking of biodynamics across entire living organisms is essential for understanding complex biology and disease progression. The presently available small‐animal functional and molecular imaging modalities remain constrained by factors including long image acquisition times, low spatial resolution, limited penetration or poor contrast. Here flash scanning volumetric optoacoustic tomography (fSVOT), a new approach for high‐speed imaging of fast kinetics and biodistribution of optical contrast agents in whole mice that simultaneously provides reference images of vascular and organ anatomy with unrivaled fidelity and contrast, is presented. The imaging protocol employs continuous overfly scanning of a spherical matrix array transducer, accomplishing a 200 µm resolution 3D scan of the whole mouse body within 45 s without relying on signal averaging. This corresponds to an imaging speed gain of more than an order of magnitude compared with existing state‐of‐the‐art implementations of comparable resolution performance. Volumetric tracking and quantification of gold nanoagent and near infrared (NIR)‐II dye kinetics and their differential uptake in various organs are demonstrated. fSVOT thus offers unprecedented capabilities for multiscale imaging of pharmacokinetics and biodistribution with high contrast, resolution, and speed.

Three-Tesla Magnetic Resonance Imaging of Patients With Deep Brain Stimulators: Results From a Phantom Study and a Pilot Study in Patients.

Deep brain stimulation (DBS) is a standard of care treatment for multiple neurologic disorders. Although 3-tesla (3T) magnetic resonance imaging (MRI) has become the gold-standard modality for structural and functional imaging, most centers refrain from 3T imaging in patients with DBS devices in place because of safety concerns. 3T MRI could be used not only for structural imaging, but also for functional MRI to study the effects of DBS on neurocircuitry and optimize programming. To use an anthropomorphic phantom design to perform temperature and voltage safety testing on an activated DBS device during 3T imaging. An anthropomorphic 3D-printed human phantom was constructed and used to perform temperature and voltage testing on a DBS device during 3T MRI. Based on the phantom assessment, a cohort study was conducted in which 6 human patients underwent MRI with their DBS device in an activated (ON) state. During the phantom study, temperature rises were under 2°C during all sequences, with the DBS in both the deactivated and activated states. Radiofrequency pulses from the MRI appeared to modulate the electrical discharge from the DBS, resulting in slight fluctuations of voltage amplitude. Six human subjects underwent MRI with their DBS in an activated state without any serious adverse events. One patient experienced stimulation-related side effects during T1-MPRAGE scanning with the DBS in an ON state because of radiofrequency-induced modulation of voltage amplitude. Following careful phantom-based safety testing, 3T structural and functional MRI can be safely performed in subjects with activated deep brain stimulators.

The role of [68\xa0Ga]Ga-DOTATATE PET/CT in wild-type KIT/PDGFRA gastrointestinal stromal tumours (GIST)

Background[68 Ga]Ga-DOTATATE PET/CT is now recognised as the most sensitive functional imaging modality for the diagnosis of well-differentiated neuroendocrine tumours (NET) and can inform treatment with peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE. However, somatostatin receptor (SSTR) expression is not unique to NET, and therefore, [68 Ga]Ga-DOTATATE PET/CT may have oncological application in other tumours. Molecular profiling of gastrointestinal stromal tumours that lack activating somatic mutations in KIT or PDGFRA or so-called ‘wild-type’ GIST (wtGIST) has demonstrated that wtGIST and NET have overlapping molecular features and has encouraged exploration of shared therapeutic targets, due to a lack of effective therapies currently available for metastatic wtGIST.AimsTo investigate (i) the diagnostic role of [68 Ga]Ga-DOTATATE PET/CT; and, (ii) to investigate the potential of this imaging modality to guide treatment with [177Lu]Lu-DOTATATE in patients with wtGIST.Methods[68 Ga]Ga-DOTATATE PET/CT was performed on 11 patients with confirmed or metastatic wtGIST and one patient with a history of wtGIST and a mediastinal mass suspicious for metastatic wtGIST, who was subsequently diagnosed with a metachronous mediastinal paraganglioma. Tumour expression of somatostatin receptor subtype 2 (SSTR2) using immunohistochemistry was performed on 54 tumour samples including samples from 8/12 (66.6%) patients who took part in the imaging study and 46 tumour samples from individuals not included in the imaging study.Results[68 Ga]Ga-DOTATATE PET/CT imaging was negative, demonstrating that liver metastases had lower uptake than background liver for nine cases (9/12 cases, 75%) and heterogeneous uptake of somatostatin tracer was noted for two cases (16.6%) of wtGIST. However, [68 Ga]Ga-DOTATATE PET/CT demonstrated intense tracer uptake in a synchronous paraganglioma in one case and a metachronous paraganglioma in another case with wtGIST.ConclusionsOur data suggest that SSTR2 is not a diagnostic or therapeutic target in wtGIST. [68 Ga]Ga-DOTATATE PET/CT may have specific diagnostic utility in differentiating wtGIST from other primary tumours such as paraganglioma in patients with sporadic and hereditary forms of wtGIST.

Whole-Head Magnetoencephalogram and Its Application in Developmental Communication Disorders Research: A Review

The human brain undergoes tremendous changes during the first decade of life. The susceptibility of the immature central nervous system to factors such as adverse environments and genetic factors is attributed to its plasticity. Neurodevelopmental disorders (NDDs) occur once the immature brain veers off the typical developmental trajectory. However, little is known about the neurophysiological traits of atypically developing children because it is challenging for them to remain still during recording. Magnetoencephalography (MEG) is a noninvasive neuroimaging technique with high-spatiotemporal resolution. An ultralow magnetic field produced by neural electrical activity can be detected using a highly sensitive whole-head magnetometer array. Current cryogenic SQUID-MEG combined with individual MRI has shown great potential in reflecting neural activity under resting states and during tasks. MEG instrumentation for children is expected to be an effective tool for investigating brain dynamics, which provides neuropsychological evidence for atypical development in communication ability. In this paper, the advantages of pediatric MEG in neurodevelopmental disorder studies are discussed first and compared with those of several noninvasive functional imaging modalities. Existing commercial pediatric MEG systems are summarized based on their respective characteristics and parameters. State-of-the-art newly emerging sensing techniques based on spin-exchange relaxation-free (SERF) along with their application in detecting infants' brain responses are introduced. Recent discoveries on MEG biomarkers in children with NDDs are then summarized concerning disorders that have comorbidities in communication, such as specific language impairment (SLI), autism spectrum disorders (ASD), dyslexia and stuttering. Progress on multimodality research and total-field wearable SERF magnetometers offers insight into the neuropsychological substrates of communication disorders.

Fusion imaging: Applications in maxillofacial radiology

Dentistry has witnessed tremendous advances in all its branches over the past three decades. With these advances, the need for more precise diagnostic tools, especially imaging modalities, has become mandatory. Many advanced imaging modalities like CT, MRI, CBCT, PET imaging are available which has made diagnostic imaging very accurate. Some of these modalities give a very good anatomic location and extent of the pathology, while others are able to image the pathology when the organ is in function. But, when both ie the precise anatomic location and functional imaging are required, than fusion of images made by more than one advanced imaging modality is required. This is where fusion imaging plays a significant role. “Fusion Imaging is the process of registering and combining multiple images from single or multiple imaging modalities to improve the imaging quality and reduce randomness and redundancy to increase the clinical applicability of medical images for diagnosis and assessment of medical problems”. It was designed to overcome the disadvantages of anatomic and functional imaging modalities and attempts to provide inputs that improve the image quality by combining the advantages of anatomic and functional imaging modalities for improvising treatment plans. The fusion imaging information is ultimate and it allows not only better understanding of various physiological and disease process but also helps in monitoring & predicting the course of the treatment and predicting the prognosis. Keywords:Fusion Imaging, PET-CT, PET-MRI, F18-FDG

Evaluation of Whole-Body MRI (WB-MRI) in Smoldering Multiple Myeloma (SMM)

Introduction Whole-body magnetic resonance imaging (WB-MRI), including multiplanar multisequence technique with diffusion weighted images, is a novel imaging technique being evaluated for patients with multiple myeloma (MM). WB-MRI is ideal for this population due to its high sensitivity for bone marrow signal changes and full anatomic coverage from vertex to mid-thighs. It is well established that patients with unequivocal focal lesions on MRI have worse outcomes. Currently the IMWG recommends that all patients with smoldering multiple myeloma (SMM) undergo WB-MRI (or whole spine MRI if WB-MRI is not available) to rule out two or more focal lesions which would classify the patient as having symptomatic myeloma requiring treatment. There is a clear benefit of using MRI for the detection of early focal myeloma lesions however less is known about findings in the SMM population. Detection of subtle findings such as one small focal lesion or heterogeneous bone marrow in WB-MRI has unknown clinical significance that needs to be further evaluated. This study aimed to evaluate the sensitivity of WB-MRI compared to other highly sensitive functional imaging modalities in patients with SMM both at baseline and after treatment. Methods Imaging of patients with WB-MRI performed at the National Institutes of Health Clinical Center Myeloma Program were reviewed and compared to whole spine MRI and 18F-FDG PET/CT completed at the same timepoint. The majority of patients were being evaluated for enrollment on clinical trials. Patients had undergone a WB-MRI with a 3-Tesla system either as a baseline study, after completion of induction treatment, or during follow up determined by the time DWI became available at our institution. The imaging protocol included sagittalT1 weighted (W) and Short tau inversion recovery (STIR) for spine and coronal, axial T1W and axial T2 TSE pulse sequences. The functional component included diffusion weighted imaging in the axial plane (b=0 and 900sec/mm2). Radiological interpretation was performed by two readers using myeloma response assessment and diagnosis system (My-RADS) {Messiou, 2019 #340}. WB-MRIs were categorized as positive if focal lesions or diffuse/heterogenous pattern of bone marrow infiltration were present. Similarly, 18F-FDG PET/CTs and whole spine MRIs were classified as positive if focal lesions or diffuse/heterogenous pattern of bone marrow were present. Results A total of 34 patients with SMM and 5 patients with relapsed refractory multiple myeloma (RRMM) had sequential WB-MRI and 18F-FDG PET/CT. Figure 1 summarizes the radiological data of the SMM population. Eleven of these patients had PET/CT, whole spine MRI, and WB-MRI at baseline. Twenty-five patients had PET/CT and WB-MRI completed after at least 8 cycles of treatment. Thirteen patients had consistently negative imaging at baseline, 7 of which also had negative imaging after treatment, while 2 patients were found to have new lesions seen on WB-MRI after treatment. Six patients had resolution of positive imaging seen at baseline after treatment. Among the 17 patients with a positive WB-MRI, 12 (71%; 95% CI 47% - 87%) had a negative correlating PET/CT. Among 5 patients with positive PET/CT at the same time point as a WB-MRI, only 1 (20%; 95% CI 2% - 64%) correlated to a negative WB-MRI. Figure 2 depicts findings from patients with RRMM for comparison. All imaging modalities showed multiple focal findings in all 5 patients. Conclusions This study depicts the high sensitivity of WB-MRI in the SMM population. Such a high sensitivity is especially needed in SMM and early myeloma when disease burden is lower and the decision for treatment is being considered. In comparison to the RRMM population where all three imaging modalities easily detect multiple focal lesions, WB-MRI tends to identify myeloma involvement in the SMM patients more than the other imaging techniques. This suggests the importance of utilizing WB-MRI when diagnosing SMM. In the SMM population, the prognostic significance of lesions that are discrepant between MRI and FDG PET/CT is not yet known. Further follow up is needed to evaluate any difference in hard endpoints such as progression free survival between patients with positive findings described by WB-MRI. Disclosures No relevant conflicts of interest to declare.

Influence of current injection scheme on electrical impedance tomography for monitoring of the respiratory function of obese subjects

Electrical impedance tomography (EIT) has been proposed as a noninvasive radiation-free functional imaging modality for bedside monitoring of lung ventilation. Due to the intrinsic low sensitivity of measured boundary voltages with respect to internal conductivity changes, EIT image reconstructions are more challenging for the regions that are located deeper from the attached surface electrodes. Considering the worldwide prevalence of obesity, it is highly desirable for an EIT system to produce high-quality images from obese as well as lean subjects. In EIT, the internal current density distribution and the sensitivity of a boundary voltage to a change of internal conductivity vary with respect to the current injection scheme. We quantified the range of measured boundary voltages subject to a chosen current injection scheme and investigated the influence of various obesity levels on the number of distinguishable boundary voltages given a fixed amount of system noise. We found that the 0-skip current injection scheme, where neighboring electrode pairs are used for current injections, could be most favorable to improve spatial resolution but produces the smallest number of distinguishable boundary voltages. To obtain an enough number of distinguishable boundary voltages from an obese subject, the gap between current injection electrodes should be increased depending on the circumference of a chosen imaging plane. We suggested a guideline for current injection schemes in EIT to produce images with better quality from obese as well as lean subjects.

Reconstruction of Endoscopic Photoacoustic Tomographic Images for Attenuating Acoustic Tissues: A Preliminary Study

Biological endoscopic photoacoustic tomography (EPAT) Has been rapidly developed in the past decades as a hybrid functional imaging modality with multi-physics coupling. The acoustic inhomogeneity of biological tissues results in acoustic reflection, scattering, diffusion and absorption, thus the attenuated photoacoustic signals measured by the detector. The idealized assumptions on the acoustic homogeneity usually lead to reconstructed images with reduced quality and imaging depth. This paper focuses on a preliminary study of EPAT image reconstruction accounting for acoustic attenuation. The correlation equation related to ideal and measured photoacoustic signals is deduced. The equation is then solved by using singular value decomposition (SVD) to recover the approximation of the ideal signals from the measured signals. Finally, the cross-sectional images of optical distribution are reconstructed from the ideal signals. Numerical results indicate that this method can effectively reduce image artifacts caused by acoustic attenuation and improve image focusing. Comparison results suggest that it outperforms the method of correcting the frequency-dependent attenuation which requires the prior knowledge about attenuation coefficients of tissues.

Generation of biological hypotheses by functional imaging links tumor hypoxia to radiation induced tissue inflammation/glucose uptake in head and neck cancer

Background and purposePositron emission tomography (PET) is a functional imaging modality which is able to deliver tracer specific biological information, e.g. about glucose uptake, inflammation or hypoxia of tumors. We performed a proof-of-principle study that used different tracers and expanded the analytical scope to non-tumor structures to evaluate tumor-host interactions. Materials and methodsBased on a previously reported prospective imaging study on 50 patients treated with curative intent chemoradiation (CRT) for head and neck squamous cell carcinoma, PET-based hypoxia and normal tissue inflammation measured by repeat 18F-fluoromisonidazole (FMISO) PET and 18F-fluorodesoxyglucose (FDG) PET, respectively, were correlated using the Spearman correlation coefficient R. PET parameters determined before and during CRT (week 1, 2 and 5), were associated with local tumor control and overall survival. ResultsTumor hypoxia at all measured times showed an inverse correlation with mid-treatment FDG-uptake of non-tumor affected oral (sub-)mucosa with R values between −0.35 and −0.6 (all p < 0.05). Mucosal FDG-uptake and mucosal hypoxia correlated positively but weaker (R values between 0.2 and 0.45). More tumor hypoxia in FMISO-PET (week 2) and less FDG-uptake of (sub-)mucosa in FDG-PET (week 4) were significantly associated with worse LC (FMISO TBRpeak: HR = 1.72, p = 0.030; FDG SUVmean: HR = 0.23, p = 0.025) and OS (FMISO TBRpeak: HR = 1.71, p = 0.007; FDG SUVmean: HR = 0.30, p = 0.003). Multivariable models including both parameters showed improved performance, suggesting that these modalities still bear distinct biological information despite their strong inter-correlation. ConclusionWe report first clinical evidence that tumor hypoxia is inversely correlated with increased FDG-uptake during radiation, potentially expressing inflammation. This observation merits further research and may have important implication for future research on tumor hypoxia and radio-immunology. Our study demonstrates that functional imaging can be utilized to assess complex tumor-host interactions and generate novel biological insights in vivo vero.