The recent introduction of high-resolution molecular imaging technology is considered by many experts as a major breakthrough that will potentially lead to a revolutionary paradigm shift in health care and revolutionize clinical practice. This paper intends to balance the capabilities of the two major molecular imaging modalities used in nuclear medicine, namely positron emission tomography (PET) and single photon emission computed tomography (SPECT). The motivations are many-fold: (1) to gain a better understanding of the strengths and limitations of the two imaging modalities in the context of recent and ongoing developments in hardware and software design; (2) to emphasize that certain issues, historically and commonly thought as limitations of one technology, may now instead be viewed as challenges that can be addressed; (3) to point out that current state of the art PET and SPECT scanners can (greatly) benefit from improvements in innovative image reconstruction algorithms; and (4) to identify important areas of research in PET and SPECT imaging that will be instrumental to further improvements in the two modalities. Both technologies are poised to advance molecular imaging and have a direct impact on clinical and research practice to influence the future of molecular medicine.

PET versus SPECT: strengths, limitations and challenges

Results from a new PET/CT scanner using lutetium-yttrium oxyorthosilicate (LYSO) crystals for the PET component are presented. This scanner, which operates in a fully 3-dimensional mode, has a diameter of 90 cm and an axial field of view of 18 cm. It uses 4 × 4 × 22 mm3 LYSO crystals arranged in a pixelated Anger-logic detector design. This scanner was designed to perform as a high-performance conventional PET scanner as well as provide good timing resolution to operate as a time-of-flight (TOF) PET scanner. Methods: Performance measurements on the scanner were made using the National Electrical Manufacturers Association (NEMA) NU2-2001 procedures to benchmark its conventional imaging capabilities. The scatter fraction and noise equivalent count (NEC) measurements with the NEMA cylinder (20-cm diameter) were repeated for 2 larger cylinders (27-cm and 35-cm diameter), which better represent average and heavy patients. New measurements were designed to characterize its intrinsic timing resolution capability, which defines its TOF performance. Additional measurements to study the impact of pulse pileup at high counting rates on timing, as well as energy and spatial, resolution were also performed. Finally, to characterize the effect of TOF reconstruction on lesion contrast and noise, the standard NEMA/International Electrotechnical Commission torso phantom as well as a large 35-cm-diameter phantom with both hot and cold spheres were imaged for varying scan times. Results: The transverse and axial resolution near the center is 4.8 mm. The absolute sensitivity of this scanner measured with a 70-cm-long line source is 6.6 cps/kBq, whereas scatter fraction is 27% measured with a 70-cm-long line source in a 20-cm-diameter cylinder. For the same line source cylinder, the peak NEC rate is measured to be 125 kcps at an activity concentration of 17.4 kBq/mL (0.47 μCi/mL). The 2 larger cylinders showed a decrease in the peak NEC due to increased attenuation, scatter, and random coincidences, and the peak occurs at lower activity concentrations. The system coincidence timing resolution was measured to be 585 ps. The timing resolution changes as a function of the singles rate due to pulse pileup and could impact TOF image reconstruction. Image-quality measurements with the torso phantom show that very high quality images can be obtained with short scan times (1–2 min per bed position). However, the benefit of TOF is more apparent with the large 35-cm-diameter phantom, where small spheres are detectable only with TOF information for short scan times. Conclusion: The Gemini TF whole-body scanner represents the first commercially available fully 3-dimensional PET scanner that achieves TOF capability as well as conventional imaging capabilities. The timing resolution is also stable over a long duration, indicating the practicality of this device. Excellent image quality is achieved for whole-body studies in 10–30 min, depending on patient size. The most significant improvement with TOF is seen for the heaviest patients.

https://jnm.snmjournals.org/content/jnumed/48/3/471.full.pdf

Performance of Philips Gemini TF PET/CT Scanner with Special Consideration for Its Time-of-Flight Imaging Capabilities

High-energy beams of charged nuclear particles (protons and heavier ions) offer significant advantages for the treatment of deep-seated local tumors in comparison to conventional megavolt photon therapy. Their physical depth-dose distribution in tissue is characterized by a small entrance dose and a distinct maximum (Bragg peak) near the end of range with a sharp fall-off at the distal edge. Taking full advantage of the well-defined range and the small lateral beam spread, modern scanning beam systems allow delivery of the dose with millimeter precision. In addition, projectiles heavier than protons such as carbon ions exhibit an enhanced biological effectiveness in the Bragg peak region caused by the dense ionization of individual particle tracks resulting in reduced cellular repair. This makes them particularly attractive for the treatment of radio-resistant tumors localized near organs at risk. While tumor therapy with protons is a well-established treatment modality with more than 60 000 patients treated worldwide, the application of heavy ions is so far restricted to a few facilities only. Nevertheless, results of clinical phase I-II trials provide evidence that carbon-ion radiotherapy might be beneficial in several tumor entities. This article reviews the progress in heavy-ion therapy, including physical and technical developments, radiobiological studiesmore » and models, as well as radiooncological studies. As a result of the promising clinical results obtained with carbon-ion beams in the past ten years at the Heavy Ion Medical Accelerator facility (Japan) and in a pilot project at GSI Darmstadt (Germany), the plans for new clinical centers for heavy-ion or combined proton and heavy-ion therapy have recently received a substantial boost.« less

Heavy-ion tumor therapy: Physical and radiobiological benefits

Significant improvements have made it possible to add the technology of time-of-flight (TOF) to improve PET, particularly for oncology applications. The goals of this work were to investigate the benefits of TOF in experimental phantoms and to determine how these benefits translate into improved performance for patient imaging. Methods: In this study we used a fully 3-dimensional scanner with the scintillator lutetium-yttrium oxyorthosilicate and a system timing resolution of ;600 ps. The data are acquired in list-mode and reconstructed with a maximum-likelihood expectation maximization algorithm; the system model includes the TOF kernel and corrections for attenuation, detector normalization, randoms, and scatter. The scatter correction is an extension of the model-based singlescatter simulation to include the time domain. Phantom measurements to study the benefit of TOF include 27-cm- and 35-cm-diameter distributions with spheres ranging in size from 10to37mm.ToassessthebenefitofTOFPETforclinicalimaging, patient studies are quantitatively analyzed. Results: The lesion phantom studies demonstrate the improved contrast of the smallest spheres with TOF compared with non-TOF and also confirm the faster convergence of contrast with TOF. These gains are evident from visual inspection of the images as well as a quantitative evaluation of contrast recovery of the spheres and noise in the background. The gains with TOF are higher for larger objects. These results correlate with patient studies in which lesions are seen more clearly and with higher uptake at comparable noise for TOF than with non-TOF. Conclusion: TOF leads to a better contrast-versus-noise trade-off than non-TOF but one that is difficult to quantify in terms of a simple sensitivity gain improvement: A single gain factor for TOF improvement does not include the increased rate of convergence with TOF nor does it consider that TOF may converge to a different contrast than non-TOF. The experimental phantom results agree with those of prior simulations and help explain the improved image quality with TOF for patient oncology studies.

https://jnm.snmjournals.org/content/jnumed/49/3/462.full.pdf

Benefit of Time-of-Flight in PET: Experimental and Clinical Results

Protons are an interesting modality for radiotherapy because of their well defined range and favourable depth dose characteristics. On the other hand, these same characteristics lead to added uncertainties in their delivery. This is particularly the case at the distal end of proton dose distributions, where the dose gradient can be extremely steep. In practice however, this gradient is rarely used to spare critical normal tissues due to such worries about its exact position in the patient. Reasons for this uncertainty are inaccuracies and non-uniqueness of the calibration from CT Hounsfield units to proton stopping powers, imaging artefacts (e.g. due to metal implants) and anatomical changes of the patient during treatment. In order to improve the precision of proton therapy therefore, it would be extremely desirable to verify proton range in vivo, either prior to, during, or after therapy. In this review, we describe and compare state-of-the art in vivo proton range verification methods currently being proposed, developed or clinically implemented.

https://iopscience.iop.org/article/10.1088/0031-9155/58/15/R131/pdf

In vivo proton range verification: a review

For the effective utilization of the favorable properties of heavy-ion beams in cancer treatment, it is important to evaluate the range of incident ions and the deposited dose distribution in a patient's body. For this purpose, the utilization of positron emitters induced in therapeutic irradiation is, at present, the only feasible method for in situ and non-invasive monitoring of heavy-ion therapy. In this study, we performed irradiation experiments with three species of ions to a water target, and the annihilation gamma-ray distributions were obtained with a positron camera. We applied the maximum likelihood estimation (MLE) method for the detected distributions to derive the range of incident ions and the deposited dose distribution in the target. As a result, the ranges were determined with a difference between the MLE range R MLE and the experimental range R exp less than 1.1 mm. The good agreement between the estimated dose distribution with the MLE method and the measured one implies that a deposited dose distribution in a target could be estimated from a detected annihilation gamma-ray distribution.

Measurements of deposited dose with induced β+ activity in proton and heavy-ion therapy

Heavy-ion radiotherapy gives a good localized dose distribution just on a cancer tumor. In order to emphasize this advantage, the verification system of a particle range and an irradiated area in a human body has been developed for the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS). The idea comes from the fact that the stopping position of a short-lived positron emitting nuclei, such as 11 C, 15 O or 19 Ne, can be precisely detected by measuring annihilation gamma-rays.

/pdf/radioactive-beam-project-at-himac-2ubgnd6nyg.pdf

Radioactive beam project at himac

A new treatment facility project, as an extension of the existing HIMAC facility, has been initiated for the further development of carbon-ion therapy. This new treatment facility will be equipped with 1) a three-dimensional irradiation system with pencil beam scanning and 2) a rotating gantry system. The design of both irradiation systems has been completed. 1) For moving-tumor treatments with high accuracy, the most important part of the design study is how to realize this by raster scanning irradiation. For this purpose, we have proposed the employment of a combination of the rescanning technique and the gated irradiation method. In order to avoid hot and/or cold spots even by a relatively larger number of rescannings within the acceptable irradiation time, we tried to develop a scanning strategy that included both the dynamic control of scanning magnets and the beam current. 2) A rotating gantry with the 2D broad-beam irradiation method as one of the possible choices for treating a moving target with existing technology was designed. In order to realize a compact design, a new method, which uses a final 90-degrees bending magnet as one of the scanner magnets, was employed. Consequently, we arrived at a total weight of about 300 tons for 400 MeV/u carbon beams with a 150 mm{sup 2} square field. (author)

Design study of scanning system and rotating gantry for HIMAC new treatment facility

高計数率に耐え得る多結晶型焦点検出器を作成し, 市販のガンマ・カメラと組み合わせてポジトロン・カメラを作成した。高速電子回路を用いた同時計数回路を用いて陽電子消滅に伴う対γ線を検出し, 位置計算をする。同時計数しない無効のγ線ががンマ・カメラに入射するのを粗い焦点型コリメータを用いて低減し, 最高計数率の改善を図るとともに, 検出効率の一様性の改善を図った。性能の概要は, (1) 最高計数率: 約2.5～4kcps, (2) 検出効率: 0.6～0.9dots/sec/μCi, (3) 位置分解能: 6～9mm (FWHM) , ( (1) ～ (3) の値はコリメー表面から線源までの距離に依存する。) , (4) 有効視野: 直径20cmの円形領域 (深さ20cmの面) である。

https://www.jstage.jst.go.jp/article/radioisotopes1952/25/11/25_11_693/_pdf

Takehiro Tomitani

Papers

Measurements of deposited dose with induced β+ activity in proton and heavy-ion therapy

Radioactive beam project at himac

Design study of scanning system and rotating gantry for HIMAC new treatment facility

A Positron Camera by Use of a Focal Detector of Hexagonal Multi-Crystal Array

Numerical Study on Range Measurement System with Positron Camera