High Resolution PET Brain Imager for Detection and Management of Alzheimer^s

描述(申请人提供)：阿尔茨海默病是一种衰弱的疾病，随着人口的继续老龄化，患病率将会增加。预计到2050年，美国将出现1600万例艾滋病病例。需要更好的分子生物标志物和分子成像仪，以便在这种可怕的疾病的最早阶段发现它，并协助开发/监测新药和治疗策略的效果。分子成像以其高度的敏感性和特异性为诊断、指导和监测阿尔茨海默氏症和其他痴呆症疾病的治疗提供了最好的机会。这些成像器需要提供高灵敏度和高分辨率。用于正电子成像(PET)或单伽马(SPECT)的标准临床核医学成像仪不能以1至几毫米的高分辨率对大脑进行成像。由于其固有的高分辨率和高效率的操作，PET是首选的检查方式。尽管用于脑成像的专用PET系统已经取得了进展，但由于探测器头的笨重尺寸，它们不便于携带，并且限制了可以进行的研究的类型。因此，我们提出了一种完全可穿戴的头盔-PET系统，使用了新的、非常紧凑的硅光电倍增技术。我们的设备将随着人的头部移动，允许人坐、站、原地跑步(在跑步机上)，甚至进行轻微的侧面运动，因此它是坐、站和有限运动的耐受性。此外，这项技术与MRI兼容，可用作MRI/fMRI成像的PET插入物。可穿戴式成像器不断地与患者的头部共同注册，从而极大地减少了运动伪影，以实现高空间分辨率扫描。此外，由于探测器模块放置在靠近大脑的位置，提高了系统效率，因此可以降低注射剂量。这将使患者能够进行更多的成像会话，而不会在跟踪疾病进展/退化、治疗监测等情况下增加辐射剂量，此外还可以降低每次扫描的成本。此外，由于部分体积效应，由于分辨率提高的间接结果，成像器对1-2 mm特征的检测灵敏度将增加一个实质性因素。我们将使用SiPM阵列与带有紧凑读出电子设备的Lyso晶体阵列相耦合，以生产内径为26厘米、最初为5厘米、最终为15厘米的多环PET成像仪。这个紧凑的环将被夹在内部和外部轻型外壳之间，以生产头盔PET脑扫描仪。该系统的重量将由适当设计的机械系统来支撑，该机械系统带有灵活的悬挂臂/缆索。该支持系统将为相关信号电缆提供从探测器模块到外部(在移动机柜中)数据采集系统的路径。最终目标是以标准PET扫描仪10倍的效率实现接近1 mm空间分辨率的实用稳健性能，同时具有可行的系统复杂性和可持续的成本。 公共卫生相关性：这项研究将有助于诊断和管理阿尔茨海默病，同时控制成本，降低患者的辐射剂量。它将允许进行过去无法进行的研究，并帮助开发新的治疗方法，以寻找治疗阿尔茨海默氏症的方法。它还可能为研究其他大脑疾病，如帕金森氏症打开大门。

DESCRIPTION (provided by applicant): Alzheimer's disease is a debilitating condition that wil increase in prevalence as the population continues to age. It is expected that the USA will see 16 million cases by 2050. There is a need for better molecular biomarkers and molecular imagers to detect this horrible disease at its earliest stages and assist with the development/monitoring of the efects of new drugs and therapeutic strategies. Molecular imaging with its high sensitivity and specificity offers the best chance to provide the necessary tools to diagnose, guide and monitor therapy of Alzheimer's and other dementia diseases. These imagers need to offer high sensitivity and high resolving power. Standard clinical nuclear medicine imagers used for positron imaging (PET) or single gamma (SPECT) are not optimized for imaging the brain at a high resolution of one to a few mm. PET is the preferred modality due to its intrinsically high resolution and high efficiency operation. Although there have been advances in specialized PET systems for brain imaging, they are not portable and limit the types of studies which can be performed due to the bulky size of the detector heads. Thus we propose a fully wearable Helmet-PET system using the new, very compact Silicon Photomultiplier technology. Our device will move with the person's head and allow the person to sit, stand, run in place (on a treadmill) and even make minor side movements, therefore it is sitting-, standing-, and limited movement- tolerant. In addition, this technology is MRI compatible and can be used as a PET insert for MRI/fMRI imaging. A wearable imager is constantly co-registered to the patient's head and thus movement artifacts are greatly minimized in order to achieve high spatial resolution scans. In addition, because of increased system efficiency with the detector modules placed close to the brain, lower injection doses are possible. This wil enable more imaging sessions for a patient without increasing the radiation dose in cases of following the progression/regression of disease, treatment monitoring, etc, in addition to lowering the cost per scan. Also, due to the Partial Volume Effect the sensitivity of the imager to detect features of 1-2mm will be increased by a substantial factor as the indirect result of the increased resolution. We will use arrays of SiPMs coupled to arrays of LYSO crystals with compact readout electronics to produce a multi-ring PET imager with a 26 cm inner diameter and initialy 5cm and ultimately 15cm in height. This compact ring will be sandwiched between inner and outer lightweight housing shells to produce a Helmet- PET brain scanner. The weight of the system will be supported by a properly designed mechanical system with a flexible suspension arm/cable. This support system will provide a path for the associated signal cables from the detector modules to the externally located (in a mobile cabinet) data acquisition system. The final goal is to achieve a practical robust performance approaching 1mm spatial resolution at 10 times the efficiency of standard PET scanners, with a viable system complexity and sustainable cost. PUBLIC HEALTH RELEVANCE: This research will help to diagnose and manage Alzheimer's disease while containing costs and lowering radiation dose to the patient. It will allow research studies which were not able to be performed in the past and assist in the development of new treatments in the search for a cure for Alzheimer's. It also may open the doors for research into other brain diseases such as Parkinson's disease.