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In the first chapter, entitled Fundamentals of Cardiac T1 Mapping, we present an overview of the scientific principles, technical choices and challenges associated with cardiac T1 mapping. This chapter reminds the reader that T1 mapping relies on a physical model of the MR signal, and shows the ways in which this model breaks down when the underlying assumptions are not met.

Objectives/Hypothesis Nasal steroids may significantly improve nasal obstructive symptoms with a reduction of adenoid size in children, but they do not consistently yield the same concurrent effect on enlarged palatine tonsils. Failure of nasal steroids to decrease the size of palatine tonsils is believed to be attributable to location and washout by saliva. The purpose of this study was to determine if direct application of steroid via intratonsillar injection would reduce the size of palatine tonsils in the rabbit model. Study Design Prospective animal study. Methods Eight rabbits (16 tonsils) were administered intratonsillar injections of fluticasone (n = 8, 1 mg/ml) or saline (n = 8, 0.1 ml) on days 0, 3, 7, 10, 14, and 17. Two rabbits (4 tonsils) received a single steroid injection to compare single versus multiple steroid injections. The rabbit's tonsil size was measured before each injection. After the fifty injections, the tonsils were harvested for histologic analysis. Results A total of 16 tonsils were analyzed. After five steroid injections, the reduction (−7.7 mm2 ± 4.27) in size was statistically significant when compared to reduction (6.12 mm2 ± 6.57) in the saline injected group (P = 0.001). Repeated steroid injection was more potent than a single injection (−3.00 mm2 ± 3.08) in reducing the size (P = 0.006). In histologic analysis, tonsils after repeated steroid injections were significantly smaller than saline-injected tonsils (P = 0.014), without obvious lymphoid follicles. Conclusion Repeated focal tonsillar injections of corticosteroids significantly reduced the size of palatine tonsils as compared to saline-injected controls. A single injection of corticosteroids appears to be effective, but not as effective, as multiple injections. Level of Evidence N/A. Laryngoscope, 124:2811–2817, 2013

Purpose There are many T1 mapping methods available, each of them validated in phantoms and reporting excellent agreement with literature. However, values in literature vary greatly, with T1 in white matter ranging from 690 to 1100 ms at 3 Tesla. This brings into question the accuracy of one of the most fundamental measurements in quantitative MRI. Our goal was to explain these variations and look into ways of mitigating them. Theory and Methods We evaluated the three most common T1 mapping methods (inversion recovery, Look-Locker, and variable flip angle) through Bloch simulations, a white matter phantom and the brains of 10 healthy subjects (single-slice). We pooled the T1 histograms of the subjects to determine whether there is a sequence-dependent bias and whether it is reproducible across subjects. Results We found good agreement between the three methods in phantoms, but poor agreement in vivo, with the white matter T1 histogram peak in healthy subjects varying by more than 30% depending on the method used. We also found that the pooled brain histograms displayed three distinct white matter peaks, with Look-Locker consistently underestimating, and variable flip angle overestimating the inversion recovery T1 values. The Bloch simulations indicated that incomplete spoiling and inaccurate B1 mapping could account for the observed differences. Conclusion We conclude that the three most common T1 mapping protocols produce stable T1 values in phantoms, but not in vivo. To improve the accuracy of T1 mapping, we recommend that sites perform in vivo validation of their T1 mapping method against the inversion recovery reference method, as the first step toward developing a robust calibration scheme. Magn Reson Med 73:514–522, 2015. © 2014 Wiley Periodicals, Inc.

Purpose: The balanced steady-state free precession (bSSFP) pulse sequence has shown to be of great interest due to its high signal-to-noise ratio efficiency. However, bSSFP images often suffer from ...

Head and neck (H&N) radiation therapy (RT) can induce irreversible damage to the salivary glands thereby causing long-term xerostomia or dry mouth in 68%–85% of the patients. Not only does xerostomia significantly impair patients’ quality-of-life (QOL) but it also has important medical sequelae, incurring high medical and dental costs. In this article, we review various measures to assess xerostomia and evaluate current and emerging solutions to address this condition in H&N cancer patients. These solutions typically seek to accomplish 1 of the 4 objectives: (1) to protect the salivary glands during RT, (2) to stimulate the remaining gland function, (3) to treat the symptoms of xerostomia, or (4) to regenerate the salivary glands. For each treatment, we assess its mechanisms of action, efficacy, safety, clinical utilization, and cost. We conclude that intensity-modulated radiation therapy is both the most widely used prevention approach and the most cost-effective existing solution and we highlight novel and promising techniques on the cost-effectiveness landscape.

Although human embryonic stem cell (hESC) hold therapeutic potential, teratoma formation has deterred clinical translation. Manganese (Mn(2+)) enters metabolically active cells through voltage-gated calcium channels and subsequently, induces T(1) shortening. We hypothesized that serial manganese-enhanced MRI would have theranostic effect to assess hESC survival, teratoma formation, and hESC-derived teratoma reduction through intracellular accumulation of Mn(2+). Firefly luciferase transduced hESCs (hESC-Lucs) were transplanted into severe combined immunodeficient mouse hindlimbs to form teratoma. The chemotherapy group was injected with MnCl(2) intraperitoneally three times a week. The control group was given MnCl(2) only prior to manganese-enhanced MRI. Longitudinal evaluation by manganese-enhanced MRI and bioluminescence imaging was performed. The chemotherapy group showed significant reduction in the teratoma volume and luciferase activity at weeks 6 and 8. Histology revealed increased proportion of dead cells and caspase 3 positive cells in the chemotherapy group. Systemic administration of MnCl(2) enabled simultaneous monitoring and elimination of hESC-derived teratoma cells by higher intracellular accumulation of Mn(2+).

Embryonic stem cells (ESCs) have shown the potential to restore cardiac function after myocardial injury. Superparamagnetic iron oxide nanoparticles (SPIO) have been widely employed to label ESCs for cellular MRI. However, nonspecific intracellular accumulation of SPIO limits long-term in vivo assessment of the transplanted cells. To overcome this limitation, a novel reporter gene (RG) has been developed to express antigens on the ESC surface. By employing SPIO-conjugated monoclonal antibody against these antigens (SPIO-MAb), the viability of transplanted ESCs can be detected in vivo. This study aims to develop a new molecular MRI method to assess in vivo ESC viability, proliferation, and teratoma formation. The RG is designed to express 2 antigens (hemagglutinin A and myc) and luciferase on the ESC surface. The two antigens serve as the molecular targets for SPIO-MAb. The human and mouse ESCs were transduced with the RG (ESC-RGs) and transplanted into the peri-infarct area using the murine myocardial injury model. In vivo MRI was performed following serial intravenous administration of SPIO-MAb. Significant hypointense signal was generated from the viable and proliferating ESCs and subsequent teratoma. This novel molecular MRI technique enabled in vivo detection of early ESC-derived teratoma formation in the injured murine myocardium.

Cell death by apoptosis is critical in myocardial diseases, and non-invasive detection of early, reversible apoptosis might be useful clinically. Exogenous Annexin-V (ANX) protein binds membrane phosphatidylserine, which is externalized in early apoptosis. A molecular MRI probe was constructed with superparamagnetic iron oxide (SPIO) conjugated to recombinant human ANX (ANX-SPIO). Apoptosis was induced with doxorubicin, a cardiotoxic cancer drug, in culture in neonatal rat ventricular myocytes, cardiac fibroblasts, and mesenchymal stem cells, and in vivo in the mouse heart. ANX-SPIO was validated using T2*-weighted 3T MRI. ANX-SPIO produced T2* signal loss, reflecting iron content, that correlated highly with independent apoptosis markers; bound with high affinity to apoptotic myocytes by competition assay (Ki 69nM); detected apoptosis in culture much earlier than did TUNEL stain; and revealed fibroblast resistance to apoptosis. With apoptosis in vivo, ANX-SPIO produced diffuse myocardial T2* signal loss that correlated with increased iron stain and caspase activity. Treatment with an alpha-1-adrenergic agonist in vivo reversed apoptosis and eliminated the ANX-SPIO MRI signal. It is concluded that cardiac MRI of ANX-SPIO detects early, non-ischemic cardiac apoptosis in culture and in vivo, and can identify reversibly injured cardiac cells in diseased hearts, when treatment is still possible.

Motion--both rigid-body and nonrigid--is the main limitation to in vivo, high-resolution larynx imaging. In this work, a new real-time motion compensation algorithm is introduced. Navigator data are processed in real time to compute the displacement information, and projections are corrected using phase modulation in k-space. Upon automatic feedback, the system immediately reacquires the data most heavily corrupted by nonrigid motion, i.e., the data whose corresponding projections could not be properly corrected. This algorithm overcomes the shortcomings of the so-called diminishing variance algorithm by combining it with navigator-based rigid-body motion correction. Because rigid-body motion correction is performed first, continual bulk motion no longer impedes nor prevents the convergence of the algorithm. Phantom experiments show that the algorithm properly corrects for translations and reacquires data corrupted by nonrigid motion. Larynx imaging was performed on healthy volunteers, and substantial reduction of motion artifacts caused by bulk shift, swallowing, and coughing was achieved.

In this article, a robust methodology for in vivo T(1) mapping is presented. The approach combines a gold standard scanning procedure with a novel fitting procedure. Fitting complex data to a five-parameter model ensures accuracy and precision of the T(1) estimation. A reduced-dimension nonlinear least squares method is proposed. This method turns the complicated multi-parameter minimization into a straightforward one-dimensional search. As the range of possible T(1) values is known, a global grid search can be used, ensuring that a global optimal solution is found. When only magnitude data are available, the algorithm is adapted to concurrently restore polarity. The performance of the new algorithm is demonstrated in simulations and phantom experiments. The new algorithm is as accurate and precise as the conventionally used Levenberg-Marquardt algorithm but much faster. This gain in speed makes the use of the five-parameter model viable. In addition, the new algorithm does not require initialization of the search parameters. Finally, the methodology is applied in vivo to conventional brain imaging and to skin imaging. T(1) values are estimated for white matter and gray matter at 1.5 T and for dermis, hypodermis, and muscle at 1.5 T, 3 T, and 7 T.

As a noninvasive modality, MR is attractive for in vivo skin imaging. Its unique soft tissue contrast makes it an ideal imaging modality to study the skin water content and to resolve the different skin layers. In this work, the challenges of in vivo high-resolution skin imaging are addressed. Three 3D Cartesian sequences are customized to achieve high-resolution imaging and their respective performance is evaluated. The balanced steady-state free precession (bSSFP) and gradient echo (GRE) sequences are fast but can be sensitive to off-resonance artifacts. The fast large-angle spin echo (FLASE) sequence provides a sharp depiction of the hypodermis structures but results in more specific absorption rate (SAR). The effect of increasing the field strength is assessed. As compared to 1.5 T, signal-to-noise ratio at 3 T slightly increases in the hypodermis and almost doubles in the dermis. The need for fat/water separation is acknowledged and a solution using an interleaved three-point Dixon method and an iterative reconstruction is shown to be effective. The effects of motion are analyzed and two techniques to prevent motion and correct for it are evaluated. Images with 117 x 117 x 500 microm(3) resolution are obtained in imaging times under 6 min.

The silicon photomultiplier (SiPM) is a novel photon detector based on Geiger mode operating avalanche photodiodes. In this paper, we present results from a test, demonstrating the feasibility of SiPM as readout elements in scintillator-based positron emission tomography (PET). As scintillator we use the newly developed LYSO crystals having similar characteristics as LSO. With our setup we measure an energy resolution of about 22% and a time resolution of a single crystal element of ( 1.51 ± 0.07 ) ns , both full-width at half-maximum. A significant improvement in time resolution could be achieved by triggering on the first photoelectron in the signal. We also present the coincidence rate of two detector channels vs. the position of a small point-like 22Na positron source.

Our research group has developed and characterized transition-edge sensor (TES) arrays for near IR-optical-near UV astrophysical observations. These detectors have a time-stamp accuracy of 0.3 μ s and an energy resolution of 0.16 eV for 2.33 eV photons at very high rates (30 kHz). We have installed a 6 × 6 array of these TESs in an adiabatic demagnetization refrigerator equipped with windows for direct imaging. We discuss new instrumentation progress and current data in all aspects related to successful operation of this camera system, including: detector and array performance, position dependence and cross-talk, low-temperature and readout electronics, quantum and system efficiency, IR filtering, and focus and imaging.

A Stanford/NIST collaboration is developing an imaging detector suitable for IR/optical/UV astronomical observations based on the Transition Edge Sensor, a cryogenic quantum microcalorimeter. Currently, the 32 pixel detector can in time and energy resolve single photons with high event rates ( Δ t 1 μ s and Δ E FWHM ∼ 0.16 eV at 2.33 eV and more than 10 kHz/pixel). We report on current progress with the first imaging TES instrument, focusing on recent advances in instrumentation including focusing, reflection masking and infrared filtering.

Background Cardiac magnetic resonance imaging has been shown to be one of the best technologies for the evaluation of cardiovascular pathologies. However, its widespread adoption has been held back by the lack of software infrastructure and specific pulse sequences that can provide a feasibly quick, comprehensive cardiac examination. We have developed an intuitive software package that can perform a comprehensive CMR examination in 30 to 45 minutes.

Nasal steroids may significantly improve nasal obstructive symptoms with a reduction of adenoid size in children, but they do not consistently yield the same concurrent effect on enlarged palatine tonsils. Failure of nasal steroids to decrease the size of palatine tonsils is believed to be attributable to location and washout by saliva. The purpose of this study was to determine if direct application of steroid via intratonsillar injection would reduce the size of palatine tonsils in the rabbit model.Prospective animal study.Eight rabbits (16 tonsils) were administered intratonsillar injections of fluticasone (n = 8, 1 mg/ml) or saline (n = 8, 0.1 ml) on days 0, 3, 7, 10, 14, and 17. Two rabbits (4 tonsils) received a single steroid injection to compare single versus multiple steroid injections. The rabbit's tonsil size was measured before each injection. After the fifty injections, the tonsils were harvested for histologic analysis.A total of 16 tonsils were analyzed. After five steroid injections, the reduction (-7.7 mm(2) ± 4.27) in size was statistically significant when compared to reduction (6.12 mm(2) ± 6.57) in the saline injected group (P = 0.001). Repeated steroid injection was more potent than a single injection (-3.00 mm(2) ± 3.08) in reducing the size (P = 0.006). In histologic analysis, tonsils after repeated steroid injections were significantly smaller than saline-injected tonsils (P = 0.014), without obvious lymphoid follicles.Repeated focal tonsillar injections of corticosteroids significantly reduced the size of palatine tonsils as compared to saline-injected controls. A single injection of corticosteroids appears to be effective, but not as effective, as multiple injections.N/A.

The balanced steady-state free precession (bSSFP) pulse sequence has shown to be of great interest due to its high signal-to-noise ratio efficiency. However, bSSFP images often suffer from banding artifacts due to off-resonance effects, which we aim to minimize in this article.We present a general and fast two-step algorithm for 1) estimating the unknowns in the bSSFP signal model from multiple phase-cycled acquisitions, and 2) reconstructing band-free images. The first step, linearization for off-resonance estimation (LORE), solves the nonlinear problem approximately by a robust linear approach. The second step applies a Gauss-Newton algorithm, initialized by LORE, to minimize the nonlinear least squares criterion. We name the full algorithm LORE-GN.We derive the Cramér-Rao bound, a theoretical lower bound of the variance for any unbiased estimator, and show that LORE-GN is statistically efficient. Furthermore, we show that simultaneous estimation of T1 and T2 from phase-cycled bSSFP is difficult, since the Cramér-Rao bound is high at common signal-to-noise ratio. Using simulated, phantom, and in vivo data, we illustrate the band-reduction capabilities of LORE-GN compared to other techniques, such as sum-of-squares.Using LORE-GN we can successfully minimize banding artifacts in bSSFP.

Motion—both rigid-body and non-rigid—is the main limitation to in vivo, high-resolution larynx imaging. In this work, a new real-time motion compensation algorithm is introduced. Navigator data are processed in real-time to compute the displacement information, and projections are corrected using phase-modulation in k-space. Upon automatic feedback, the system immediately reacquires the data most heavily corrupted by non-rigid motion, i.e., the data whose corresponding projections could not be properly corrected. This algorithm overcomes the shortcomings of the so-called Diminishing Variance Algorithm (DVA) by combining it with navigator-based rigid-body motion correction. Because rigid-body motion correction is performed first, continual bulk motion no longer impedes nor prevents the convergence of the algorithm. Phantom experiments show that the algorithm properly corrects for translations and reacquires data corrupted by non-rigid motion. Larynx imaging was performed on healthy volunteers, and substantial reduction of motion artifacts caused by bulk shift, swallowing, and coughing was achieved.

As a noninvasive modality, MR is attractive for in vivo skin imaging. Its unique soft tissue contrast makes it an ideal imaging modality to study the skin water content and to resolve the different skin layers. In this work, the challenges of in vivo high-resolution skin imaging are addressed. Three 3D Cartesian sequences are customized to achieve high-resolution imaging and their respective performance is evaluated. The balanced steady-state free precession (bSSFP) and gradient echo (GRE) sequences are fast but can be sensitive to off-resonance artifacts. The fast large-angle spin echo (FLASE) sequence provides a sharp depiction of the hypodermis structures but results in more specific absorption rate (SAR). The effect of increasing the field strength is assessed. As compared to 1.5 T, signal-to-noise ratio at 3 T slightly increases in the hypodermis and almost doubles in the dermis. The need for fat/water separation is acknowledged and a solution using an interleaved three-point Dixon method and an iterative reconstruction is shown to be effective. The effects of motion are analyzed and two techniques to prevent motion and correct for it are evaluated. Images with 117 x 117 x 500 microm(3) resolution are obtained in imaging times under 6 min.

2) FeCo/GC nanocrystals Composed of an iron-cobalt core encapsulated by a biocompatible graphite shell (size 7 nm) with Cy5.5 attached for fluorescence imaging. FeCo/GC have superior MRI properties with both cellular imaging and heating attributes. A higher dose (25 mgFe/kg) was used for detection at 3 T than 7 T (6 mgFe/kg). 3) MRI 2 weeks post-ligation, mice (n = 4) were imaged on a whole-body 3 T MRI scanner (Signa HDx, GE Healthcare) with installed gradients (50 mT/m, 150 T/m/s) and a custom 3 cm surface RF coil. As a comparison, another group of mice (n = 3) were imaged on a small-bore 7 T system (30 cm bore magnet, Varian Inc. plus GE "Micro-Signa" environment), with a 9 cm gradient insert (770 mT/m, and 2500 T/m/s, Resonance Research, Inc.) and a custom 6-cm RF coil. Similar gradient echo sequences were used (3 T: TR/TE = 100 ms/10 ms, slice thickness = 1.0 mm, from 13th Annual SCMR Scientific Sessions Phoenix, AZ, USA. 21-24 January 2010

The reconstruction of artifact-free images from truncated datasets poses a challenging problem in any medical imaging modality. Such a problem occurs in Projection Reconstruction MRI when the object is not fully encompassed within the FOV. This is always the case for coronal and sagittal planes in extremity imaging. Introduced recently in CT and SPECT, the derivative back projection-finite Hilbert inverse (DBP-FHI) algorithm has been proven useful to accurately reconstruct from truncated datasets within regions-of-interest. Here, we propose an adaptation of the DBP-FHI algorithm to handle PR-MRI data. Details of the underlying theory and its discrete implementation are explained. Numerical simulations show that shading artifacts present when the image is reconstructed with filtered back projection (FBP) disappear with this new algorithm. In vivo phantom and knee scans demonstrate that truncation artifacts resulting from the FBP algorithm are mitigated by the DBP-FHI algorithm. Within geometric constraints, the proposed algorithm always outperforms the FBP algorithm by its ability to reconstruct truncated datasets.

The silicon photomultiplier (SiPM) is a novel photon detector based on Geiger mode operating avalanche photodiodes. In this paper we present experimental results which show that SiPMs can be used in positron emission tomography (PET). As scintillator we use the newly developed LYSO material, which has very similar characteristics to the widely used LSO. With our setup we measure an energy resolution of (21.5/spl plusmn/0.5)% and a coincidence time resolution of (1.51/spl plusmn/0.07) ns, both full width at half maximum. A significant improvement in time resolution could be achieved by triggering on the first photoelectron in the signal. We also present the coincidence rate of two detector channels vs. the position of a small pointlike /sup 22/Na positronium source.

Background Doxorubicin (DOX) is a widely used chemotherapy drug that causes irreversible cardiomyopathy in a growing number of patients. An early detection method for this side effect could positively impact patient care. Previous work validated a molecular MRI probe that linked human Annexin V (ANX), a protein that binds strongly to early apoptotic cells, to superparamagnetic iron oxide (SPIO). T2 weighted (T2W) cardiac MRI of ANX-SPIO was found to detect DOX-induced cardiac apoptosis in mice. Alpha-1AR adrenergic stimulation with A61603 (A6) has been shown to prevent DOX-induced apoptosis and cardiac dysfunction in mice.