Sweep Imaging With Fourier Transformation Research Articles

Low field slice-selective ZTE imaging of ultra-short T_2 tissues based on spin-locking

Magnetic Resonance Imaging of hard biological tissues is very challenging due to small proton abundance and ultra-short T_2 decay times, especially at low magnetic fields, where sample magnetization is weak. While several pulse sequences, such as Ultra-short Echo Time (UTE), Zero Echo Time (ZTE) and SWeep Imaging with Fourier Transformation (SWIFT), have been developed to cope with ultra-short lived MR signals, only the latter two hold promise of imaging tissues with sub-millisecond T_2 times at low fields. All these sequences are intrinsically volumetric, thus 3D, because standard slice selection using a long soft radio-frequency pulse is incompatible with ultra-short lived signals. The exception is UTE, where double half pulses can perform slice selection, although at the cost of doubling the acquisition time. Here we demonstrate that spin-locking is a versatile and robust method for slice selection for ultra-short lived signals, and present three ways of combining this pulse sequence with ZTE imaging of the selected slice. With these tools, we demonstrate slice-selected 2D ex vivo imaging of the hardest tissues in the body at low field (260 mT) within clinically acceptable times.

Event-recurring multiband SWIFT functional MRI with 200-ms temporal resolution during deep brain stimulation and isoflurane-induced burst suppression in rat.

To develop a high temporal resolution functional MRI method for tracking repeating events in the brain. We developed a novel functional MRI method using multiband sweep imaging with Fourier transformation (SWIFT), termed event-recurring SWIFT (EVER-SWIFT). The method is able to image similar repeating events with subsecond temporal resolution. Here, we demonstrate the use of EVER-SWIFT for detecting functional MRI responses during deep brain stimulation of the medial septal nucleus and during spontaneous isoflurane-induced burst suppression in the rat brain at 9.4 T with 200-ms temporal resolution. The EVER-SWIFT approach showed that the shapes and time-to-peak values of the response curves to deep brain stimulation significantly differed between downstream brain regions connected to the medial septal nucleus, resembling findings obtained with traditional 2-second temporal resolution. In contrast, EVER-SWIFT allowed for detailed temporal measurement of a spontaneous isoflurane-induced bursting activity pattern, which was not achieved with traditional temporal resolution. The EVER-SWIFT technique enables subsecond 3D imaging of both stimulated and spontaneously recurring brain activities, and thus holds great potential for studying the mechanisms of neuromodulation and spontaneous brain activity.

Bright ultrashort echo time SWIFT MRI signal at the osteochondral junction is not located in the calcified cartilage.

In this study, we aimed to precisely localize the hyperintense signal that is generated at the osteochondral junction when using ultrashort echo time magnetic resonance imaging (MRI) and to investigate the osteochondral junction using sweep imaging with Fourier transformation (SWIFT) MRI. Furthermore, we seek to evaluate what compositional properties of the osteochondral junction are the sources of this signal. In the study, we obtained eight samples from a tibial plateau dissected from a 68-year-old male donor, and one additional osteochondral sample of bovine origin. The samples were imaged using high-resolution ultrashort echo time SWIFT MRI and microcomputed tomography (μCT) scans. Localization of the bright signal in the osteochondral junction was performed using coregistered data sets. Potential sources of the signal feature were examined by imaging the bovine specimen with variable receiver bandwidths and by performing variable flip angle T1 relaxation time mapping. The results of the study showed that the hyperintense signal was found to be located entirely in the deep noncalcified articular cartilage. The intensity of this signal at the interface varied between the specimens. Further tests with bovine specimens indicated that the imaging bandwidth and T1 relaxation affect the properties of the signal. Based on the present results, the calcified cartilage has low signal intensity even in SWIFT imaging. Concomitantly, it appears that the bright signal seen in ultrashort echo time imaging resides within the noncalcified cartilage. Furthermore, the most likely sources of this signal are the rapid T1 relaxation of the deep cartilage and the susceptibility-induced effects arising from the calcified tissues.

Magnetic Resonance Imaging of Hard Tissues and Hard Tissue Engineered Bio-substitutes

Magnetic resonance imaging (MRI) is a non-invasive diagnostic imaging tool based on the detection of protons into the tissues. This imaging technique is remarkable because of high spatial resolution, strong soft tissue contrast and specificity, and good depth penetration. However, MR imaging of hard tissues, such as bone and teeth, remains challenging due to low proton content in such tissues as well as to very short transverse relaxation times (T2). To overcome these issues, new MRI techniques, such as sweep imaging with Fourier transformation (SWIFT), ultrashort echo time (UTE) imaging, and zero echo time (ZTE) imaging, have been developed for hard tissues imaging with promising results reported. Within this article, MRI techniques developed for the detection of hard tissues, such as bone and dental tissues, have been reviewed. The main goal was thus to give a comprehensive overview on the corresponding (pre-) clinical applications and on the potential future directions with such techniques applied. In addition, a section dedicated to MR imaging of novel biomaterials developed for hard tissue applications was given as well.

MRI: PROMISING DENTAL APPLICATIONS THAT SUGGEST CLINICAL UTILITY

Background Magnetic resonance imaging (MRI) research at the University of Minnesota has resulted in notable advancements, including capture of signal from densely calcified tissues. Application of this technology to address dental questions plus efforts to minimize the cost and size of MRI scanners suggests the potential adoption of MRI in regular clinical dental settings. Objective This abstract reviews advances in the areas that move this technology closer to adoption in dentistry: (1) capture of quickly decaying T2 signal, (2) coil development for dental applications, and (3) redesign of the MRI scanner for cost/size reductions. We present recent data suggesting that existing MRI technology can detect (cracks and blood flow within teeth. Materials and Methods Twenty-nine human teeth extracted after clinical diagnosis of a root crack/fracture were frequency matched to 29 control teeth. Teeth were scanned with MRI and cone beam computed tomography (CBCT). A 4-member panel evaluated the images according to established criteria. Saline was pumped through microtubing inserted into an extracted tooth to resemble pulpal blood flow. Flow rates were controlled within the range of calculated rates of pulpal arterioles. The setup was imaged with a sweep imaging with Fourier transformation (SWIFT)-MRI saturation technique to distinguish the moving fluid from surrounding stationary fluid. Results CBCT and MRI demonstrated similar levels of sensitivity and specificity, despite nonoptimized MRI image processing and limited observer calibration. Images with selective saturation of flowing or still liquids allowed for successful visualization of fluid-flow through the extracted tooth. Discussion Using improved pre- and postprocessing MRI approaches, teeth should be rescanned to enhance sensitivity of detecting cracks. Panelists should be educated and calibrated, and a reliability assessment study should be performed again with a larger sample size. Studies in extracted tooth flow imaging should be conducted to determine the lower limit of flow detection and whole-dentition in vivo images of vascular flow in teeth obtained.

Imaging of a high concentration of iron labeled cells with positive contrast in a rat knee.

The sweep imaging with Fourier transformation (SWIFT) imaging technique has been shown to provide positive contrast from diluted cell suspensions labeled with super-paramagnetic iron oxide (SPIO) in a tissue, as an alternative to T2*-weighted imaging. Here we demonstrate a variation of the SWIFT technique that yields a hyperintense signal from a concentrated cell suspension. The proposed technique provides minimal background signal from host tissue and facilitates visualization of injected cells. The proton resonance frequency and linewidth were determined for SPIO solutions of different concentrations. The original SWIFT sequence was modified and a dual saturation Gaussian shape RF pulse with ~200 Hz bandwidth was incorporated into the acquisition protocol to suppress host tissue and fat signals. This modification of the original acquisition protocol permits the detection of a hyperintense signal from grafted cells with minimal background signal from the host tissue. SPIO particles not only induce broadening of NMR line-width but also an initiate proton resonance frequency shift. This shift is linearly proportional to the concentration of the iron oxide particles and induced by the bulk magnetic susceptibility of SPIOs. The shift of the resonance frequency of iron labeled cells allowed us effectively suppress the host tissues with saturation RF pulse to improve MRI detection of grafted cells. Iron oxide particles increase the resonance frequency of water proton signal. This shift permitted us to add the tissue/fat saturation RF pulse into the original SWIFT acquisition protocol and detect distinct hyperintense signals from grafted cells with minimal background signal from the host tissue.

Positive contrast from cells labeled with iron oxide nanoparticles: Quantitation of imaging data.

Conventional T2 -weighted MRI produces a hypointense signal from iron-labeled cells, which renders quantification unfeasible. We tested a SWeep Imaging with Fourier Transformation (SWIFT) MRI pulse sequence to generate a quantifiable hyperintense signal from iron-labeled cells. Mesenchymal stem cells (MSCs) were labeled with different concentrations of iron oxide particles and examined for cell viability, proliferation, and differentiation. The SWIFT sequence was optimized to detect and quantify the amount of iron in the muscle tissue after injection of iron oxide solution and iron-labeled MSCs. The incubation of MSCs with iron oxide and low concentration of poly-L-lysine mixture resulted in an internalization of up to 22 pg of iron per cell with no adverse effect on MSCs. Phantom experiments showed a dependence of SWIFT signal intensity on the excitation flip angle. The hyperintense signal from iron-labeled cells or solutions was detected, and an amount of the iron oxide in the tissue was quantified with the variable flip angle method. The SWIFT sequence can produce a quantifiable hyperintense MRI signal from iron-labeled cells. The graft of 18 x 106 cells was detectable for 19 days after injection and the amount of iron was quantifiable. The proposed protocol simplifies the detection and provides a means to quantify cell numbers. Magn Reson Med 78:1900-1910, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Magnetization transfer SWIFT MRI consistently detects histologically verified myelin loss in the thalamocortical pathway after a traumatic brain injury in rat.

Traumatic brain injury (TBI) is associated with various neurocognitive deficits, and rapid assessment of the damage is potentially important for the prevention and treatment of these deficits. Imaging assessment of mild or moderate damage outside the primary lesion area after TBI, however, remains challenging. Magnetization transfer (MT) has clearly been underutilized in imaging the damage caused by TBI. Here, we applied the MT ratio (MTR) using sweep imaging with Fourier transformation (SWIFT) to study microstructural tissue damage in the thalamocortical pathway outside the primary lesion in a lateral fluid percussion injury rat model of TBI, 5months after injury. MTR was decreased in layers VIb-IV of the barrel cortex and related subcortical areas, mainly indicating demyelination, which was verified by histology. The largest MTR change in the cortex was in layer VIb (-8.2%, pFDR =0.01), and the largest MTR change in the subcortical areas was in the caudal-most portion of the internal capsule (-11.0%, pFDR <0.005). These areas exhibited the greatest demyelination and substantial cellularity attributed to gliosis. Correlation analysis of group-averaged results from the subcortical areas revealed an excellent correlation of MTR with myelin (r2 =0.94, p<0.001), but no correlation with increased cellularity as detected by Nissl staining. Thus, MTR using SWIFT can be a valuable tool for the assessment of subtle changes after TBI in both cortical and subcortical areas.

Abstract 4248: Functional imaging markers for blockade of breast cancer metastasis by IGF1R and insulin receptor targeted drugs using novel MRI and targeted iron oxide nanoparticles

Abstract IGF1R and insulin receptor (IR) regulate biology of estrogen positive (ER+) and triple negative breast cancer (TNBC) cells. The results of initial clinical trials with anti-IGF1R drugs have been disappointing due to feedback upregulation of insulin receptor (IR) signaling and absence of biomarkers for these drugs. We evaluated the effects of BMS-754807, a dual tyrosine kinase inhibitor of IGF1R/IR on ER+ and TNBC. In ER+ MCF-7 cells, it inhibited xenograft growth of MCF-7 tumors (n = 10 per treatment) compared to vehicle. Interestingly, while tumor growth was suppressed over a period of five weeks, eventually the tumors displayed resistance to BMS-754807. In TNBC, it inhibited motility in vitro. In contrast to ER+ cells, BMS-754807 did not inhibit primary tumor growth of TNBC cells injected into the mammary fat pad of mice. But at a dose of 50 mg/kg daily inhibited metastasis of TNBC cells, MDA-231-LM2 and MDA-MB435A/LCC6 cells, in the orthotopic and tail vein models of metastasis compared to vehicle (n = 10/group). Our data indicate that regulation of metastasis and tumor growth by IGF1R can be discrete events and functional imaging to identify biological properties of metastatic breast cancer regulated by IGF1R/IR are needed to better define treatments. While MRI is a powerful tool for detecting and imaging cancer, its utility in imaging metastasis to the lung is limited due to the challenges of lung MRI with conventional 3D gradient echo (GRE). MRI does not visualize lung well, mainly due to the abundance of air-tissue interfaces, which cause the MR signal to decay too rapidly for conventional MRI pulse sequences to capture. Clinically metastases are monitored by CT or PET but exposure of patients to ionizing radiation is a concern and problematic in longitudinal studies monitoring response to a targeted drug. Therefore, we recently reported the utility of a novel MR sequence called sweep imaging with Fourier transformation (SWIFT), where the data is acquired quasi-simultaneously with the radiofrequency pulse, to image lung metastasis of breast cancer. Here, we monitored response to IGF1R and IGF1R/IR targeted drugs in preclinical models of lung metastasis of breast cancer. We used MDA-231-LM2 cells with the tail vein injection model of metastasis. Mice with breast cancer metastases in the lungs were treated with either huEM164, an antibody against IGF1R, or BMS-754807. Metastasis was monitored by BLI and SWIFT MRI weekly. SWIFT was more sensitive in detecting inhibition of metastasis by these drugs. Thus, dual inhibition of IGF1R and IR is effective in blocking growth of ER+ and metastasis of TNBC. However, combination of this therapeutic strategy with other agents may be necessary to prevent or delay onset of resistance. Further, noninvasive biomarkers of response to IGF1R/IR targeted drugs can be developed with SWIFT imaging. Citation Format: Deepali Sachdev, Huy Donguyen, Naoharu Kobayashi, Sidath C. Kumarapperuma, Joeseph C. Weber. Functional imaging markers for blockade of breast cancer metastasis by IGF1R and insulin receptor targeted drugs using novel MRI and targeted iron oxide nanoparticles. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4248.

Abstract P1-07-03: Dual inhibition of IGF1R and insulin receptor in estrogen receptor positive and triple negative breast cancer and monitoring blockade of metastasis using novel MRI

Abstract Insulin-like growth factors (IGFs) and insulin acting via the type I IGF receptor (IGF1R) and insulin receptor (IR) respectively regulate biology of estrogen positive (ER+) and triple negative (TN) breast cancer cells. In animal models, inhibition of IGF1R alone with antibodies has demonstrated significant inhibition of tumor growth and/or metastasis of several types of cancer cells. Unfortunately, the results of initial clinical trials with anti-IGF1R antibodies have been disappointing. One reason for this is that inhibition of the related IR through which insulin and IGF-II signal, may be necessary for optimal efficacy of this targeted approach. Second, there is a need to develop markers that can be used to stratify patients who may benefit from these drugs and/or monitor response to these drugs. To examine the effectiveness of dual inhibition of IGF1R and IR, we evaluated the effects of BMS-754807, a small molecule dual tyrosine kinase inhibitor of IGF1R/IR on ER+ and TN breast cancer cells. In ER+ cells (MCF-7, T47D and ZR-75-1), BMS-754807 inhibited IGF-I, IGF-II and insulin stimulated activation of downstream PI3K and MAPK pathways, proliferation and anchorage-independent growth in vitro. BMS-754807 also blocked signaling in MCF-7 tumors and inhibited xenograft growth of MCF-7 tumors (n=10 per treatment) compared to vehicle. Interestingly, while tumor growth was suppressed over a period of five weeks, eventually the tumors displayed resistance to BMS-754807. In TN cell lines (MDA-MB-231; MDA-MB-231-LM2 and MDA-231-BoM, lung seeking and bone specific metastatic variants respectively of MDA-MB-231; and MDA-MB435A/LCC6) BMS-754807 also inhibited activation of the PI3K pathway and motility in vitro. In contrast to ER+ cells, BMS-754807 did not inhibit primary tumor growth of TN breast cancers cells injected into the mammary fat pad of mice. But BMS-754807 (50 mg/kg daily by oral gavage) inhibited metastasis of TN cells, MDA-231-LM2 and MDA-MB435A/LCC6 cells, in the orthotopic and tail vein models of metastasis compared to vehicle (n=10/group). Our data indicate that regulation of metastases and tumor growth by IGF1R can be discrete events and functional imaging to identify biological properties of metastatic breast cancer regulated by IGF1R/IR are needed to better define treatments. Therefore, we used a novel MR sequence called sweep imaging with Fourier transformation (SWIFT), where the data is acquired quasi-simultaneously with the radiofrequency pulse, to monitor response to BMS-754807. We used MDA-231-LM2 cells with the tail vein injection model of metastasis. Mice injected with breast cancer cells were treated with either vehicle or BMS-754807 and metastasis was monitored by BLI and SWIFT MRI weekly. SWIFT was sensitive in detecting inhibition of metastasis by BMS-754807. Our results suggest that dual inhibition of IGF1R and IR is effective in blocking growth of ER+ and metastasis of TN breast cancers. However, combination of this therapeutic strategy with other agents may be necessary to prevent or delay onset of resistance. Further, noninvasive biomarkers of response to IGF1R/IR targeted drugs can be developed with SWIFT imaging. Citation Format: Deepali Sachdev, Joel D Winer, Naoharu Kobayashi, Michael Garwood, Joseph Weber. Dual inhibition of IGF1R and insulin receptor in estrogen receptor positive and triple negative breast cancer and monitoring blockade of metastasis using novel MRI [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-07-03.

Gradient-modulated SWIFT.

Methods designed to image fast-relaxing spins, such as sweep imaging with Fourier transformation (SWIFT), often utilize high excitation bandwidth and duty cycle, and in some applications the optimal flip angle cannot be used without exceeding safe specific absorption rate (SAR) levels. The aim is to reduce SAR and increase the flexibility of SWIFT by applying time-varying gradient-modulation (GM). The modified sequence is called GM-SWIFT. The method known as gradient-modulated offset independent adiabaticity was used to modulate the radiofrequency (RF) pulse and gradients. An expanded correlation algorithm was developed for GM-SWIFT to correct the phase and scale effects. Simulations and phantom and in vivo human experiments were performed to verify the correlation algorithm and to evaluate imaging performance. GM-SWIFT reduces SAR, RF amplitude, and acquisition time by up to 90%, 70%, and 45%, respectively, while maintaining image quality. The choice of GM parameter influences the lower limit of short T2 (*) sensitivity, which can be exploited to suppress unwanted image haze from unresolvable ultrashort T2 (*) signals originating from plastic materials in the coil housing and fixatives. GM-SWIFT reduces peak and total RF power requirements and provides additional flexibility for optimizing SAR, RF amplitude, scan time, and image quality.

3D Cine Magnetic Resonance Imaging of Rat Lung ARDS using Gradient-modulated SWIFT with Retrospective Respiratory Gating.

SWeep Imaging with Fourier Transformation (SWIFT) with gradient modulation and DC navigator retrospective gating is introduced as a 3D cine magnetic resonance imaging (MRI) method for the lung. The quasi-simultaneous excitation and acquisition in SWIFT enabled extremely high sensitivity to the fast-decaying parenchymal signals (TE=~4 μs), which are invisible with conventional MRI techniques. Based on respiratory motion information extracted from DC navigator signals, the SWIFT data were reconstructed to 3D cine images with 16 respiratory phases. To test the capability of the proposed technique, rats exposed to > 95% O2 for 60 hours for induction of acute respiratory distress syndrome (ARDS), were imaged and compared with normal rat lungs (N=7 and 5 for ARDS and normal group, respectively). SWIFT images showed lung tissue density difference along the gravity direction. In the cine SWIFT images, parenchymal signal drop at the inhalation phase was consistently observed for both normal and ARDS rats due to inflation of the lung (i.e. decrease of the proton density), but the drop was less for ARDS rats. Depending on the respiration phase and lung region, the lungs from the ARDS rats showed 1-24% higher parenchymal signal intensities relative to the normal rat lungs, which would be mainly from accumulation of extravascular water (EVLW). Those results demonstrate that SWIFT has high enough sensitivity for detecting the lung proton density changes due to gravity, different respiration phases and accumulation of EVLW in the rat ARDS lungs.

Multi-Band-SWIFT

A useful extension to SWIFT (SWeep Imaging with Fourier Transformation) utilizing sidebands of the excitation pulse is introduced. This MRI method, called Multi-Band-SWIFT, achieves much higher bandwidth than standard SWIFT by using multiple segmented excitations (bands) of the field of view. A description of the general idea and variants of the pulse sequence are presented. From simulations and semi-phenomenological theory, estimations of power deposition and signal-to-noise ratio are made. MB-SWIFT and ZTE (zero-TE) sequences are compared based on images of a phantom and human mandible. Multi-Band-SWIFT provides a bridge between SWIFT and ZTE sequences and allows greatly increased excitation and acquisition bandwidths relative to standard SWIFT for the same hardware switching parameters and requires less peak amplitude of the radiofrequency field (or greater flip angle at same peak amplitude) as compared to ZTE. Multi-Band-SWIFT appears to be an attractive extension of SWIFT for certain musculoskeletal and other medical imaging applications, as well as for imaging materials.

High-spatial- and high-temporal-resolution dynamic contrast-enhanced MR breast imaging with sweep imaging with Fourier transformation: a pilot study.

To report the results of sweep imaging with Fourier transformation (SWIFT) magnetic resonance (MR) imaging for diagnostic breast imaging. Informed consent was obtained from all participants under one of two institutional review board-approved, HIPAA-compliant protocols. Twelve female patients (age range, 19-54 years; mean age, 41.2 years) and eight normal control subjects (age range, 22-56 years; mean age, 43.2 years) enrolled and completed the study from January 28, 2011, to March 5, 2013. Patients had previous lesions that were Breast Imaging Reporting and Data System 4 and 5 based on mammography and/or ultrasonographic imaging. Contrast-enhanced SWIFT imaging was completed by using a 4-T research MR imaging system. Noncontrast studies were completed in the normal control subjects. One of two sized single-breast SWIFT-compatible transceiver coils was used for nine patients and five controls. Three patients and five control subjects used a SWIFT-compatible dual breast coil. Temporal resolution was 5.9-7.5 seconds. Spatial resolution was 1.00 mm isotropic, with later examinations at 0.67 mm isotropic, and dual breast at 1.00 mm or 0.75 mm isotropic resolution. Two nonblinded breast radiologists reported SWIFT image findings of normal breast tissue, benign fibroadenomas (six of six lesions), and malignant lesions (10 of 12 lesions) concordant with other imaging modalities and pathologic reports. Two lesions in two patients were not visualized because of coil field of view. The images yielded by SWIFT showed the presence and extent of known breast lesions. The SWIFT technique could become an important addition to breast imaging modalities because it provides high spatial resolution at all points during the dynamic contrast-enhanced examination.

Chaotic Compressed Sensing and Its Application to Magnetic Resonance Imaging

Fast image acquisition in magnetic resonance imaging (MRI) is important, due to the need to find ways that help relieve patient’s stress during MRI scans. Methods for fast MRI have been proposed, most notably among them are pMRI (parallel MRI), SWIFT (SWeep Imaging with Fourier Transformation), and compressed sensing (CS) based MRI. Although it promises to significantly reduce acquisition time, applying CS to MRI leads to difficulties with hardware design because of the randomness nature of the measurement matrix used by the conventional CS methods. In this paper, we propose a novel method that combines the above-mentioned three approaches for fast MRI by designing a compound measurement matrix from a series of single measurement matrices corresponding to pMRI, SWIFT, and CS. In our method, the CS measurement matrix is designed to be deterministic via chaotic systems. This chaotic compressed sensing (CCS) measurement matrix, while retaining most features of the random CS matrix, is simpler to realize in hardware. Several compound measurement matrices have been constructed and examined in this work, including CCS-MRI, CCS-pMRI, CCS-SWIFT, and CCS-pSWIFT. Simulation results showed that the proposed method allows an increase in the speed of the MRI acquisition process while not compromising the quality of the acquired MR images.

SWIFT MRI enhances detection of breast cancer metastasis to the lung.

To evaluate the capability of longitudinal MR scans using sweep imaging with Fourier transformation (SWIFT) to detect breast cancer metastasis to the lung in mice. Mice with breast cancer metastatic to the lung were generated by tail vein injection of MDA-MB-231-LM2 cells. Thereafter, MR imaging was performed every week using three different pulse sequences: SWIFT [echo time (TE) ∼3 μs], concurrent dephasing and excitation (CODE; TE ∼300 μs), and three-dimensional (3D) gradient echo (GRE; TE = 2.2 ms). Motion during the long SWIFT MR scans was compensated for by rigid-body motion correction. Maximum intensity projection (MIP) images were generated to visualize changes in lung vascular structures during the development and growth of metastases. SWIFT MRI was more sensitive to signals from the lung parenchyma than CODE or 3D GRE MRI. Metastatic tumor growth in the lungs induced a progressive increase in intensity of parenchymal signals in SWIFT images. MIP images from SWIFT clearly visualized lung vascular structures and their disruption due to progression of breast cancer metastases in the lung. SWIFT MRI's sensitivity to fast-decaying signals and tolerance of magnetic susceptibility enhances its effectiveness at detecting structural changes in lung parenchyma and vasculature due to breast cancer metastases in the lung.

Quantifying iron‐oxide nanoparticles at high concentration based on longitudinal relaxation using a three‐dimensional SWIFT look‐locker sequence

PurposeIron‐oxide nanoparticles (IONPs) have proven utility as contrast agents in many MRI applications. Previous quantitative IONP mapping has been performed using mainly T2* mapping methods. However, in applications requiring high IONP concentrations, such as magnetic nanoparticles based thermal therapies, conventional pulse sequences are unable to map T2* because the signal decays too rapidly. In this article, sweep imaging with Fourier transformation (SWIFT) sequence is combined with the Look‐Locker method to map T1 of IONPs in high concentrations.MethodsT1 values of agar containing IONPs in different concentrations were measured with the SWIFT Look‐Locker method and with inversion recovery spectroscopy. Precisions of Look‐Locker and variable flip angle (VFA) methods were compared in simulations.ResultsThe measured R1 (=1/T1) has a linear relationship with IONP concentration up to 53.6 mM of Fe. This concentration exceeds concentrations measured in previous work by almost an order of magnitude. Simulations show SWIFT Look‐Locker method is also much less sensitive to B1 inhomogeneity than the VFA method.ConclusionSWIFT Look‐Locker can accurately measure T1 of IONP concentrations ≤53.6 mM. By mapping T1 as a function of IONP concentration, IONP distribution maps might be used in the future to plan effective magnetic nanoparticle hyperthermia therapy. Magn Reson Med 71:1982–1988, 2014. © 2014 Wiley Periodicals, Inc.

Quantifying iron‐oxide nanoparticles at high concentration based on longitudinal relaxation using a three‐dimensional SWIFT look‐locker sequence

Iron-oxide nanoparticles (IONPs) have proven utility as contrast agents in many MRI applications. Previous quantitative IONP mapping has been performed using mainly T2 * mapping methods. However, in applications requiring high IONP concentrations, such as magnetic nanoparticles based thermal therapies, conventional pulse sequences are unable to map T2 * because the signal decays too rapidly. In this article, sweep imaging with Fourier transformation (SWIFT) sequence is combined with the Look-Locker method to map T1 of IONPs in high concentrations. T1 values of agar containing IONPs in different concentrations were measured with the SWIFT Look-Locker method and with inversion recovery spectroscopy. Precisions of Look-Locker and variable flip angle (VFA) methods were compared in simulations. The measured R1 (=1/T1 ) has a linear relationship with IONP concentration up to 53.6 mM of Fe. This concentration exceeds concentrations measured in previous work by almost an order of magnitude. Simulations show SWIFT Look-Locker method is also much less sensitive to B1 inhomogeneity than the VFA method. SWIFT Look-Locker can accurately measure T1 of IONP concentrations ≤53.6 mM. By mapping T1 as a function of IONP concentration, IONP distribution maps might be used in the future to plan effective magnetic nanoparticle hyperthermia therapy.

Gap cycling for SWIFT

SWIFT (SWeep Imaging with Fourier Transformation) is a non-Cartesian MRI method with unique features and capabilities. In SWIFT, radiofrequency (RF) excitation and reception are performed nearly simultaneously, by rapidly switching between transmit and receive during a frequency-swept RF pulse. Because both the transmitted pulse and data acquisition are simultaneously amplitude-modulated in SWIFT (in contrast to continuous RF excitation and uninterrupted data acquisition in more familiar MRI sequences), crosstalk between different frequency bands occurs in the data. This crosstalk leads to a "bulls-eye" artifact in SWIFT images. We present a method to cancel this interband crosstalk by cycling the pulse and receive gap positions relative to the un-gapped pulse shape. We call this strategy "gap cycling." We carry out theoretical analysis, simulation and experiments to characterize the signal chain, resulting artifacts, and their elimination for SWIFT. Theoretical analysis reveals the mechanism for gap-cycling's effectiveness in canceling interband crosstalk in the received data. We show phantom and in vivo results demonstrating bulls-eye artifact free images. Gap cycling is an effective method to remove bulls-eye artifact resulting from interband crosstalk in SWIFT data.

Abstract P4-01-19: Enhanced sensitivity to detect metastases of breast cancer to the lung and monitor response to inhibition of metastasis by IGF1R inhibitor using SWIFT MRI

Abstract Breast cancers metastasize to the bone, lung, brain and liver and mortality from breast cancer is due to metastases. Drugs that inhibit metastasis in particular of triple negative (TN) breast cancers, more sensitive methods to image metastases and imaging biomarkers to monitor response to these drugs at sites of metastasis are needed to reduce mortality. The type I insulin-like growth factor receptor (IGF1R) regulates metastasis and drugs targeting IGF1R and or insulin receptor inhibit metastasis of TN breast cancer cells in mouse models. The initial clinical trials of these drugs have not been very successful and point to the need to develop imaging biomarkers for this therapy. While MRI is a powerful tool for detecting and imaging cancer, its utility in imaging metastasis to the lung is limited due to the challenges of lung MRI with conventional 3D gradient echo (GRE). MRI does not visualize lung well, mainly due to the abundance of air-tissue interfaces, which cause the MR signal to decay too rapidly for conventional MRI pulse sequences to capture. Clinically lung metastases are monitored by CT or PET but exposure of patients to ionizing radiation is a concern and problematic in longitudinal studies monitoring response to a targeted drug. Further MRI can also be useful in measuring metabolite levels using MR spectroscopy (MRS). Therefore, we evaluated the capability of a novel MR sequence called sweep imaging with Fourier transformation (SWIFT), where the data is acquired concurrently with the radiofrequency pulse, to detect breast cancer metastases to lung and test if inhibition of metastases by an IGF1R targeted drug can be monitored by SWIFT. We used the tail vein injection model of breast cancer metastasis with MDA-MB-231-LM2, a lung-seeking metastatic TN breast cancer cell line. Lung metastases were monitored with bioluminescence imaging (BLI) and MRI every week. MRI was done with two pulse sequences: SWIFT (with a short echo time or TE∼3 μs) and GRE (with a longer TE = 2.2 ms). SWIFT showed significantly higher sensitivity in detecting signals from lung parenchyma compared to GRE and structural information was visible in the area of the lungs. Metastatic tumor growth in the lung induced a progressive increase in signal from the lung parenchyma in SWIFT images. MIP images from SWIFT clearly visualized the lung vascular structures and their disruption due to progression of breast cancer metastasis. To test if SWIFT can also be useful in monitoring inhibition of metastases, mice injected with cells were treated with either vehicle or an IGF1R inhibitor (huEM164) twice a week. When inhibition of metastases in the huEM164 treated group compared to the vehicle group was evident by BLI, MR images were acquired. SWIFT was sensitive in detecting the inhibition of metastases by the IGF1R antibody. Our data show that high sensitivity to fast-decaying signals and tolerance to the magnetic susceptibility in SWIFT enhance the capability to detect signal and structural changes in the lung parenchyma and vasculature due to metastasis of breast cancer. Further, SWIFT was also sensitive to monitor inhibition of metastasis in response to IGF1R targeted drugs. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-01-19.