Proton Imaging Technique Research Articles

Review of oxygen-enhanced lung mri: Pulse sequences for image acquisition and T1 measurement.

Oxygen-enhanced MR imaging (OE-MRI) is a special proton imaging technique that can be performed without modifying the scanner hardware. Many fundamental studies have been conducted following the initial reporting of this technique in 1996, illustrating the high potential for its clinical application. This review aims to summarise and analyse current pulse sequences and T1 measurement methods for OE-MRI, including fundamental theories, existing pulse sequences applied to OE-MRI acquisition and T1 mapping. Wash-in and wash-out time identify lung function and are sensitive to ventilation; thus, dynamic OE-MRI is also discussed in this review. We compare OE-MRI with the primary competitive technique, hyperpolarised gas MRI. Finally, an overview of lower-field applications of OE-MRI is highlighted, as relatively recent publications demonstrated positive results. Lower-field OE-MRI, which is lower than 1.5 T, could be an alternative modality for detecting lung diseases. This educational review is aimed at researchers who want a quick summary of the steps needed to perform pulmonary OE-MRI with a particular focus on sequence design, settings, and quantification methods.

Design of a compact proton beam energy modulator for imaging

Proton beam therapy is the current state of the art for irradiation of cancerous tumors near vital organs. Proton imaging is a new technology that images tumors with the same particle interaction as proton therapy, promising more accurate treatment preparation compared to traditional computerized tomography scans. A specific proton imaging technique in development at Massachusetts General Hospital requires an energy modulator that can fit inside the gantry nozzle. This work presents the design of a compact proton beam energy modulator required for such imaging applications. A combination of steel and lead wedges was used to create a balanced modulation wheel, with an axis of rotation perpendicular to the incident beam. The mechanical design also allows interchangeable disks and precise position control. The modulator design was verified by testing on a proton beam line. The final device achieved a wide range of energy modulation (21 cm water-equivalent thickness) while maintaining a constant exiting beam angular spread meeting device requirements. This compact design facilitates proton imaging to be practically incorporated into future gantry systems, which will advance proton treatment for tumors near vital organs.

Investigation of time-resolved proton radiography using x-ray flat-panel imaging system

Proton beam therapy benefits from the Bragg peak and delivers highly conformal dose distributions. However, the location of the end-of-range is subject to uncertainties related to the accuracy of the relative proton stopping power estimates and thereby the water-equivalent path length (WEPL) along the beam. To remedy the range uncertainty, an in vivo measurement of the WEPL through the patient, i.e. a proton-range radiograph, is highly desirable. Towards that goal, we have explored a novel method of proton radiography based on the time-resolved dose measured by a flat panel imager (FPI).A 226 MeV pencil beam and a custom-designed range modulator wheel (MW) were used to create a time-varying broad beam. The proton imaging technique used exploits this time dependency by looking at the dose rate at the imager as a function of time. This dose rate function (DRF) has a unique time-varying dose pattern at each depth of penetration. A relatively slow rotation of the MW (0.2 revolutions per second) and a fast image acquisition (30 frames per second, ~33 ms sampling) provided a sufficient temporal resolution for each DRF. Along with the high output of the CsI:Tl scintillator, imaging with pixel binning (2 × 2) generated high signal-to-noise data at a very low radiation dose (~0.1 cGy).Proton radiographs of a head phantom and a Gammex CT calibration phantom were taken with various configurations. The results of the phantom measurements show that the FPI can generate low noise and high spatial resolution proton radiographs. The WEPL values of the CT tissue surrogate inserts show that the measured relative stopping powers are accurate to ~2%. The panel did not show any noticeable radiation damage after the accumulative dose of approximately 3831 cGy. In summary, we have successfully demonstrated a highly practical method of generating proton radiography using an x-ray flat panel imager.

Magnetic field generation during intense laser channelling in underdense plasma

Channel formation during the propagation of a high-energy (120 J) and long duration (30 ps) laser pulse through an underdense deuterium plasma has been spatially and temporally resolved via means of a proton imaging technique, with intrinsic resolutions of a few μm and a few ps, respectively. Conclusive proof is provided that strong azimuthally symmetric magnetic fields with a strength of around 0.5 MG are created inside the channel, consistent with the generation of a collimated beam of relativistic electrons. The inferred electron beam characteristics may have implications for the cone-free fast-ignition scheme of inertial confinement fusion.

Dynamics of Self-Generated, Large Amplitude Magnetic Fields Following High-Intensity Laser Matter Interaction

The dynamics of magnetic fields with an amplitude of several tens of megagauss, generated at both sides of a solid target irradiated with a high-intensity (~10(19) W/cm(2)) picosecond laser pulse, has been spatially and temporally resolved using a proton imaging technique. The amplitude of the magnetic fields is sufficiently large to have a constraining effect on the radial expansion of the plasma sheath at the target surfaces. These results, supported by numerical simulations and simple analytical modeling, may have implications for ion acceleration driven by the plasma sheath at the rear side of the target as well as for the laboratory study of self-collimated high-energy plasma jets.

SU‐E‐J‐168: Proton Radiography for Pediatric, T‐Spine and Lung Malignancies; Development and Enhancement of a Proton Imaging Technique

Purpose: Proton radiography (PR) was investigated for daily set up prior to proton radiation treatment, which would provide improved imaging capabilities along with reduced radiation dose to pediatric, lung and T‐spine tumors. Pediatric patients are more susceptible to radiation induced malignancies and toxicities from therapeutic and diagnostic radiation. While, in the case of T‐spine and lung tumors, motion and lung heterogeneities can significantly reduce the benefit of using proton beam therapy. Methods: A group of 5 pediatric patients with 1) neuroblastoma, 2) spinal malignancy, or 3) thoracic tumor were used to evaluate proton radiography. In addition, 7 lung/T‐spine tumors were also used to evaluate the ability of proton radiography to allow real‐time tumor tracking, while the tumor is moving within the lung with the patient respiration. Proton radiographic images were generated using a Monte Carlo imaging tool, PR‐Imaging, developed at MGH. Results: Radiographic images of the lung tumors were generated with simulated PR‐Imaging using a scanned proton pencil beam (PBS) at 230MeV, 330MeV and 490MeV, and compared to diagnostic X‐ray digitally reconstructed radiographs (DRR). In addition, whole body PR‐Images of pediatrics was compared to conventional X‐ray radiographs. PR images with high resolution comparable to that of a diagnostic x‐ray were generated. The X‐ray portal images and the X‐ray radiographs present better edge detection, while lung tissue to soft tissue boundaries of the tumor were better distinguished in PR images. The PR‐imaging allows the oncologist and radiologist to change windowing level and tumor contrast level relative to soft tissue background. Conclusions: PR‐Imaging prior to therapy allows for high quality images that can provide information on range degradation of the proton therapy beam. PR‐Imaging during therapy allows for daily quality assurance and tumor tracking during radiation to guarantee that it has been appropriately treated with radiation.

Non-invasive magnetic resonance thermography during regional hyperthermia

Regional hyperthermia is a non-invasive technique in which cancer tissue is exposed to moderately high temperatures of approximately 43–45°C. The clinical delivery of hyperthermia requires control of the temperatures applied. This is typically done using catheters with temperature probes, which is an interventional procedure. Additionally, a catheter allows temperature monitoring only at discrete positions. These limitations can be overcome by magnetic resonance (MR) thermometry, which allows non-invasive mapping of the entire treatment area during hyperthermia application.Various temperature-sensitive MRI parameters exist and can be exploited for MR temperature mapping. The most popular parameters are proton resonance frequency shift (PRFS) (Δφ corresponding to a frequency shift of 0.011 ppm, i.e. 0.7 Hz per °C at 1.5 Tesla), diffusion coefficient D (ΔD/D = 2–3 % per °C), longitudinal relaxation time T1 ( per °C), and equilibrium magnetisation M0 ( per °C). Additionally, MRI temperature mapping based on temperature-sensitive contrast media is applied. The different techniques of MRI thermometry were developed to serve different purposes.The PRFS method is the most sensitive proton imaging technique. A sensitivity of ±0.5°C is possible in vivo but use of PRFS imaging remains challenging because of a high sensitivity to susceptibility effects, especially when field homogeneity is poor, e.g. on interventional MR scanners or because of distortions caused by an inserted applicator. Diffusion-based MR temperature mapping has an excellent correlation with actual temperatures in tissues. Correct MR temperature measurement without rescaling is achieved using the T1 method, if the scaling factor is known. MR temperature imaging methods using exogenous temperature indicators are chemical shift and 3D phase sensitive imaging. TmDOTMA− appears to be the most promising lanthanide complex because it showed a temperature imaging accuracy of <0.3°C.

Application of proton radiography in experiments of relevance to inertial confinement fusion

Multi-Mev proton beams generated by target normal sheath acceleration (TNSA) during the interaction of an ultra intense laser beam (I≥1019 W/cm2) with a thin metallic foil (thickness of the order of a few tens of microns) are particularly suited as a particle probe for laser plasma experiments. The proton imaging technique employs a laser-driven proton beam in a point-projection imaging scheme as a diagnostic tool for the detection of electric fields in such experiments. The proton probing technique has been applied in experiments of relevance to inertial confinement fusion (ICF) such as laser heated gasbags and laser-hohlraum experiments. The data provides direct information on the onset of laser beam filamentation and on the plasma expansion in the hohlraum’s interior, and confirms the suitability and usefulness of this technique as an ICF diagnostic.

Propagation of relativistic electrons in low density foam targets

The propagation of laser-driven, relativistic electron beams in plasmas is a phenomenon of relevance to applications such as the Fast Ignition of fusion targets. In this paper, we report on experiments where the transport of hot electron currents through foam targets has been studied using the proton imaging technique. Strong filamentation has been observed, possibly due to electromagnetic instabilities of the Weibel type. The experiments were performed at the RAL Petawatt laser facility.

Transient electric fields in laser plasmas observed by proton streak deflectometry

A novel proton imaging technique was applied which allows a continuous temporal record of electric fields within a time window of several nanoseconds. This “proton streak deflectometry” was used to investigate transient electric fields of intense (∼1017W∕cm2) laser irradiated foils. We found out that these fields with an absolute peak of up to 108V∕m extend over millimeter lateral extension and decay at nanosecond duration. Hence, they last much longer than the (approximately picosecond) laser excitation and extend much beyond the laser irradiation focus.

High-intensity laser-plasma interaction studies employing laser-driven proton probes

Due to their particular properties (low emittance, short duration, and large number density), the beams of multi-MeV protons generated during the interaction of ultraintense (I &gt; 1019 W/cm2) short pulses with thin solid targets are suited for use as a particle probe in laser-plasma experiments. When traversing a sample, the proton density distribution is, in general, affected by collisional stopping, scattering and deflections via electromagnetic fields, and each of these effects can be used for diagnostic purposes. In particular, in the limit of very thin targets, the proton beams represent a valuable diagnostic tool for the detection of quasi-static electromagnetic fields. The proton imaging and deflectometry techniques employ these beams, in a point-projection imaging scheme, as an easily synchronizable diagnostic tool in laser- plasma interactions, with high temporal and spatial resolution. By providing diagnostic access to electro-magnetic field distributions in dense plasmas, this novel diagnostics opens up to investigation a whole new range of unexplored phenomena. Several transient processes were investigated employing this technique, via the detection of the associated electric fields. Examples provided in this paper include the detection of pressure-gradient electric field in extended plasmas, and the study of the electrostatic fields associated to the emission of MeV proton beams in high-intensity laser-foil interactions.

Plasma Ion Evolution in the Wake of a High-Intensity Ultrashort Laser Pulse

Experimental investigations of the late-time ion structures formed in the wake of an ultrashort, intense laser pulse propagating in a tenuous plasma have been performed using the proton imaging technique. The pattern found in the wake of the laser pulse shows unexpectedly regular modulations inside a long, finite width channel. On the basis of extensive particle in cell simulations of the plasma evolution in the wake of the pulse, we interpret this pattern as due to ion modulations developed during a two-stream instability excited by the return electric current generated by the wakefield.

Quantitative analysis of proton imaging measurements of laser-induced plasmas

A method for obtaining quantitative information about electric field and charge distributions from proton imaging measurements of laser-induced plasmas is presented. A parameterised charge distribution is used as target plasma. The deflection of a proton beam by the electric field of such a plasma is simulated numerically as well as the resulting proton density, which will be obtained on a screen behind the plasma according to the proton imaging technique. The parameters of the specific charge distributions are delivered by a combination of linear regression and nonlinear fitting of the calculated proton density distribution to the measured optical density of a radiochromic film screen changed by proton exposure. It is shown that superpositions of spherical Gaussian charge distributions as target plasma are sufficient to simulate various structures in proton imaging measurements, which makes this method very flexible.

Dynamics of relativistic solitons

Relativistic solitons are self-trapped, finite-sized, electromagnetic waves of relativistic intensity that propagate without diffraction spreading. They have been predicted theoretically within the relativistic fluid approximation, and have been observed in multi-dimensional particle-in-cell simulations of laser pulse interaction with the plasma. Solitons were observed in laser irradiated plasmas with the proton imaging technique as well. This paper reviews many theoretical results on relativistic solitons in electron–ion plasmas.

Molecular imaging with endogenous substances.

Dynamic nuclear polarization has enabled hyperpolarization of nuclei such as 13C and 15N in endogenous substances. The resulting high nuclear polarization makes it possible to perform subsecond 13C MRI. By using the dynamic nuclear polarization hyperpolarization technique, 10% polarization was obtained in an aqueous solution of 100 mM 13C-labeled urea, ready for injection. The in vivo T1 relaxation time of 13C in the urea solution was determined to 20 +/- 2 s. Due to the long relaxation time, it is possible to use the hyperpolarized substance for medical imaging. A series of high-resolution ( approximately 1-mm) magnetic resonance images were acquired, each with a scan time of 240 ms, 0-5 s after an i.v. injection of the hyperpolarized aqueous [13C]urea solution in a rat. The results show that it is possible to perform 13C angiography with a signal-to-noise ratio of approximately 275 in approximately 0.25 s. Perfusion studies with endogenous substances may allow higher spatial and/or temporal resolution than is possible with current proton imaging techniques.

Proton imaging detection of transient electromagnetic fields in laser-plasma interactions (invited)

Due to their particular properties (small source size, low divergence, short duration, large number density), the beams of multi-MeV protons generated during the interaction of ultraintense (I&amp;gt;1019 W/cm2) short pulses with thin solid targets are most suited for use as a particle probe in laser–plasma experiments. In particular, the proton beams are a valuable diagnostic tool for the detection of electromagnetic fields. The recently developed proton imaging technique employs the beams, in a point-projection imaging scheme, as an easily synchronizable diagnostic tool in laser–plasma interactions, fields, with high temporal and spatial resolution. The broad energy spectrum of the beams coupled with an appropriate choice of detector (multiple layers of dosimetric film) allows temporal multiframe capability. By allowing, for the first time, diagnostic access to electric-field distributions in dense plasmas, this novel diagnostic opens up to investigation a whole new range of unexplored phenomena. Results obtained in experiments performed at the Rutherford Appleton Laboratory are discussed here. In particular, the article presents the measurement of highly transient electric fields related to the generation and dynamics of hot electron currents following ultraintense laser irradiation of targets. The experimental capabilities of the technique and the analysis procedure required are well exemplified by the data presented.

Electric field detection in laser-plasma interaction experiments via the proton imaging technique

Due to their particular properties, the beams of the multi-MeV protons generated during the interaction of ultraintense (I&amp;gt;1019 W/cm2) short pulses with thin solid targets are most suited for use as a particle probe in laser-plasma experiments. The recently developed proton imaging technique employs the beams in a point-projection imaging scheme as a diagnostic tool for the detection of electric fields in laser-plasma interaction experiments. In recent investigations carried out at the Rutherford Appleton Laboratory (RAL, UK), a wide range of laser-plasma interaction conditions of relevance for inertial confinement fusion (ICF)/fast ignition has been explored. Among the results obtained will be discussed: the electric field distribution in laser-produced long-scale plasmas of ICF interest; the measurement of highly transient electric fields related to the generation and dynamics of hot electron currents following ultra-intense laser irradiation of targets; the observation in underdense plasmas, after the propagation of ultra-intense laser pulses, of structures identified as the remnants of solitons produced in the wake of the pulse.

In vivo NMR imaging and spectroscopic investigation of renal pathology in lean and obese rat kidneys

Diabetic nephropathy is a major cause of end-stage renal failure. While our understanding of the pathogenesis of nephropathy is incomplete, progressive glomerular injury appears to play a significant role in the decline of renal function. Proton NMR spectroscopy and imaging techniques were used to address changes in renal pathology associated with glomerular mesangial expansion in vivo in kidneys from spontaneously obese and lean (control) littermate Zucker rats. Fully functioning rat kidneys were surgically exposed and externalized for direct NMR signal detection via a coil placed around the organ. High-resolution (78 microns in plane) proton images were obtained at 4.7 T magnetic field strength revealing fine structure within the well-defined cortical and medullary regions. The obese rat kidney images were distinct in appearance from the lean kidney images and exhibited marked cortical expansion as well as increased overall kidney size. Enlargement of mean glomerular diameter was verified histologically in the obese kidneys as compared with the lean kidneys. Proton T1 and T2 relaxation times were determined from the entire kidney using standard spectroscopic techniques, and from specific regions within the kidney from multiple T1- and T-2 weighted images. Additionally, image contrast enhancement resulting from saturation transfer between protons in restricted-mobility environments and mobile water protons within the kidney was investigated in the lean and obese rat kidneys using magnetization-transfer imaging techniques. At the early stage of renal injury examined in this study, diseased and healthy kidneys could not be differentiated on the basis of relaxation times alone. The magnitude of saturation transfer obtained in cortical tissue in the lean and obese kidneys was also not statistically significantly different. However, the magnitude of saturation transfer achieved in the medullary tissue of obese kidneys was statistically significantly less than that achieved in lean kidneys.

Magnetic Resonance Imaging and 31P Spectroscopy of an Interictal Cortical Spike Focus in the Rat

Magnetic resonance imaging (MRI) has proven to be an effective noninvasive technique for identifying lesions in patients with temporal lobe epilepsy. It has also been suggested that MRI may be sensitive to transient functional or metabolic changes in brain tissue. Increased brain electrical activity as monitored by electroencephalography causes changes in cerebral metabolism that may be responsible for focal or regional alterations in signal in the MRI of some patients. To test this hypotheses, experimental interictal cortical foci were produced in rats by topical application of penicillin to one hemisphere of the brain. In vivo MRI and phosphorous-31 (31P) spectroscopy of the focal and contralateral hemifield were performed in a 30-cm bore 1.89-T Bruker MSL system. 31P spectroscopy revealed no quantifiable differences in pH or in phosphocreatinine and ATP levels between the focal area and the contralateral hemisphere or between experimental and saline-treated control animals. There were also no differences in proton MRI. Similar areas of prolonged T2 were found near the cortex and in the deeper parenchyma in 55% of the experimental animals and 50% of the controls. These results suggest that the electrical activity from an interictal cortical spike focus is not severe enough to perturb cerebral metabolism sufficiently to be detectable by 31P spectroscopy or proton imaging techniques.

Reproducibility of relaxation and spin-density parameters in phantoms and the human brain measured by MR imaging at 1.5 T.

The reproducibility of T1, T2, and proton density, measured in phantoms and the human brain was evaluated by proton imaging techniques. The sequence used to derive T1 and density values was a multiple-saturation recovery which consists of four pairs of 90 degrees pulses, followed by a 180 degrees phase reversal pulse, generating four T1-weighted images. T2 was derived from a multiple-echo sequence, generating four T2-weighted images. The data were analyzed by fitting the pixel intensities to the respective equations by means of nonlinear multiparameter least-squares analysis. Short-term reproducibility between four consecutive scans was evaluated to be 1-4% depending on location with a phantom covering the entire span of physiologic T1 and T2 values. A second phantom containing a series of identical samples served to study the dependence of the apparent T1 and T2 on position, both radially and axially, with respect to magnet isocenter. Reproducibility across the field of view was found to be better than 7% (T1 and T2). This phantom was further used to evaluate effects of long-term reproducibility, which at each location varied from 5-14% (T1) and 2-10% (T2). Finally, interinstrument reproducibility, tested by means of the same protocol on three different instruments, all operating at the same magnetic field and using largely identical hardware for each location, was found to be 1-14% (T1) and 2-10% (T2). The positional dependence of the apparent relaxation times appears to be systematic and may be due to variations in the effective field, caused by magnet and rf inhomogeneity. Finally, brain tissue relaxation and spin-density data were determined using the same protocol in 37 scans performed on 27 normal volunteers. The tissues analyzed were putamen, thalamus, caudate nucleus, centrum semiovale, internal capsule, and corpus callosum. Excellent accordance was further obtained between left and right hemispheres.