A phosphatase gene is linked to nectar dihydroxyacetone accumulation in manuka (Leptospermum scoparium).

Floral nectar composition beyond common sugars shows great diversity but contributing genetic factors are generally unknown. Manuka (Leptospermum scoparium) is renowned for the antimicrobial compound methylglyoxal in its derived honey, which originates from the precursor, dihydroxyacetone (DHA), accumulating in the nectar. Although this nectar trait is highly variable, genetic contribution to the trait is unclear. Therefore, we investigated key gene(s) and genomic regions underpinning this trait. We used RNAseq analysis to identify nectary-associated genes differentially expressed between high and low nectar DHA genotypes. We also used a manuka high-density linkage map and quantitative trait loci (QTL) mapping population, supported by an improved genome assembly, to reveal genetic regions associated with nectar DHA content. Expression and QTL analyses both pointed to the involvement of a phosphatase gene, LsSgpp2. The expression pattern of LsSgpp2 correlated with nectar DHA accumulation, and it co-located with a QTL on chromosome 4. The identification of three QTLs, some of the first reported for a plant nectar trait, indicates polygenic control of DHA content. We have established plant genetics as a key influence on DHA accumulation. The data suggest the hypothesis of LsSGPP2 releasing DHA from DHA-phosphate and variability in LsSgpp2 gene expression contributing to the trait variability.

Practical Overview of 123I-Ioflupane Imaging in Parkinsonian Syndromes.

Parkinsonian syndromes are a heterogeneous group of progressive neurodegenerative disorders involving the nigrostriatal dopaminergic pathway and are characterized by a wide spectrum of motor and nonmotor symptoms. These syndromes are quite common and can profoundly impact the lives of patients and their families. In addition to classic Parkinson disease, parkinsonian syndromes include multiple additional disorders known collectively as Parkinson-plus syndromes or atypical parkinsonism. These are characterized by the classic parkinsonian motor symptoms with additional distinguishing clinical features. Dopamine transporter SPECT has been developed as a diagnostic tool to assess the levels of dopamine transporters in the striatum. This imaging assessment, which uses iodine 123 (123I) ioflupane, can be useful to differentiate parkinsonian syndromes caused by nigrostriatal degeneration from other clinical mimics such as essential tremor or psychogenic tremor. Dopamine transporter imaging plays a crucial role in diagnosing parkinsonian syndromes, particularly in patients who do not clearly fulfill the clinical criteria for diagnosis. Diagnostic clarification can allow early treatment in appropriate patients and avoid misdiagnosis. At present, only the qualitative interpretation of dopamine transporter SPECT is approved by the U.S. Food and Drug Administration, but quantitative interpretation is often used to supplement qualitative interpretation. The authors provide an overview of patient preparation, common imaging findings, and potential pitfalls that radiologists and nuclear medicine physicians should know when performing and interpreting dopamine transporter examinations. Alternatives to 123I-ioflupane imaging for the evaluation of nigrostriatal degeneration are also briefly discussed. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Intenzo and Colarossi in this issue.

Utility of SPECT Functional Neuroimaging of Pain.

Functional neuroimaging modalities vary in spatial and temporal resolution. One major limitation of most functional neuroimaging modalities is that only neural activation taking place inside the scanner can be imaged. This limitation makes functional neuroimaging in many clinical scenarios extremely difficult or impossible. The most commonly used radiopharmaceutical in Single Photon Emission Tomography (SPECT) functional brain imaging is Technetium 99 m-labeled Ethyl Cysteinate Dimer (ECD). ECD is a lipophilic compound with unique pharmacodynamics. It crosses the blood brain barrier and has high first pass extraction by the neurons proportional to regional brain perfusion at the time of injection. It reaches peak activity in the brain 1 min after injection and is then slowly cleared from the brain following a biexponential mode. This allows for a practical imaging window of 1 or 2 h after injection. In other words, it freezes a snapshot of brain perfusion at the time of injection that is kept and can be imaged later. This unique feature allows for designing functional brain imaging studies that do not require the patient to be inside the scanner at the time of brain activation. Functional brain imaging during severe burn wound care is an example that has been extensively studied using this technique. Not only does SPECT allow for imaging of brain activity under extreme pain conditions in clinical settings, but it also allows for imaging of brain activity modulation in response to analgesic maneuvers whether pharmacologic or non-traditional such as using virtual reality analgesia. Together with its utility in extreme situations, SPECTS is also helpful in investigating brain activation under typical pain conditions such as experimental controlled pain and chronic pain syndromes.

Production of Betacyanins in Transgenic Nicotiana tabacum Increases Tolerance to Salinity.

Although red betalain pigments (betacyanins) have been associated with salinity tolerance in some halophytes like Disphyma australe, efforts to determine whether they have a causal role and the underlying mechanisms have been hampered by a lack of a model system. To address this, we engineered betalain-producing Nicotiana tabacum, by the introduction of three betalain biosynthetic genes. The plants were violet-red due to the accumulation of three betacyanins: betanin, isobetanin, and betanidin. Under salt stress, betacyanic seedlings had increased survivability and leaves of mature plants had higher photochemical quantum yields of photosystem II (F v /F m ) and faster photosynthetic recovery after saturating light treatment. Under salt stress, compared to controls betacyanic leaf disks had no loss of carotenoids, a slower rate of chlorophyll degradation, and higher F v /F m values. Furthermore, simulation of betacyanin pigmentation by using a red filter cover improved F v /F m value of green tissue under salt stress. Our results confirm a direct causal role of betacyanins in plant salinity tolerance and indicate a key mechanism is photoprotection. A role in delaying leaf senescence was also indicated, and the enhanced antioxidant capability of the betacyanic leaves suggested a potential contribution to scavenging reactive oxygen species. The study can inform the development of novel biotechnological approaches to improving agricultural productivity in saline-affected areas.

The Role of the Cerebellum in Pain Perception: A Brain SPECT Perfusion Study in Patients with Burn Injuries.

BACKGROUND AND PURPOSE: Virtual reality (VR) is a promising tool for distraction analgesia. This study aims to compare brain perfusion patterns while patients were undergoing burn wound care in two conditions-VR distraction and control (NoVR). METHODS: With IRB approval, four patients hospitalized for acute burn care (three males and one female) participated in the study. All patients underwent wound care on two consecutive days; 1 day with standard analgesia and adjunctive VR, and the other day with standard analgesia alone, otherwise the wound care was very similar. Tc-99m ethyl cysteinate dimer was injected during wound care at the time of peak pain. Subjective patient reports on a 0-10 scale of pain intensity, time spent thinking about pain, and "fun" as well as opioid equivalent usage were analyzed. Voxel by voxel subtraction analysis of brain perfusion Single Photon Emission Computed Tomography (SPECT) images was performed at the group level. Statistical significance threshold was defined as P < .05. RESULTS: Mean group subjective scores (VR, NoVR, statistical significance, and P-value) were observed for maximal pain intensity (9.0, 8.8, insignificant, and P = .809), time spent thinking about pain (5.2, 10.0, significant, and P = .015), and fun (6.0, 2.5, significant, and P = .012). Subtraction group analysis demonstrated VR-induced modulation of brain activity with statistically significant relative suppression of cerebellar activation in the VR compared to intense cerebellar activation in the NoVR environments. CONCLUSION: Relative decrease in cerebellar perfusion based on stringent statistical threshold in the VR environment combined with improved subjective pain experience supports the hypotheses on the role of cerebellum in perception of noxious stimuli.

Virtual Reality to Relieve Pain in Burn Patients Undergoing Imaging and Treatment.

Pain from burn injuries is among the most excruciating encountered in clinical practice. Pharmacological methods often fail to achieve acceptable level of analgesia in these patients, especially during burn wound dressing and debridement. Virtual reality (VR) distraction is a promising analgesic technique that progressed significantly in the last decade with development of commercially available, low-cost, high-resolution, wide field-of-view, standalone VR devices that can be used in many clinical scenarios. VR has demonstrated clinical benefit as an adjunctive analgesic during burn wound dressing and other painful medical procedures. The technique has proven useful also in preparing patients for magnetic resonance imaging scans, particularly in claustrophobic patients. Modulation of pain-related brain activity at cortical and subcortical levels by VR, and its correlation with subjective improvement in various laboratory and clinical pain experiences has been demonstrated using multiple functional brain imaging studies including functional magnetic resonance imaging and brain perfusion single photon emission computed tomography.

Impact of decompressive craniectomy on brain perfusion scintigraphy as an ancillary test for brain death diagnosis.

OBJECTIVES: Decompressive craniectomy is occasionally performed for patients with impending brain death, which is intended to relieve critically elevated intracranial pressure to keep effective intracranial perfusion. It has been in debate if this surgery later affects the result of brain perfusion scintigraphy performed as an ancillary test in the course of brain death diagnosis because rigid closed skull is deemed essential to elevate intracranial pressure to the point of total absence of intracranial radiotracer uptake on scintigraphy. The purpose of this study is to elucidate the impact of decompressive craniectomy on the result of brain perfusion scintigraphy in patients with suspected brain death. METHODS: This retrospective cross-sectional study included consecutive 151 brain perfusion scintigraphy performed in 138 patients with suspected brain death from various causes (male 82 patients, female 56 patients; range 0-74 years; mean age 36.6 years). All exams were indicated due to inconclusive clinical diagnosis of brain death. The scintigraphy protocol consists of immediate flow phase and delayed parenchymal phase planar imaging. Additional SPECT imaging was performed in 15 studies in 14 patients. The results, positive or negative brain flow, were compared between patients with and without decompressive craniectomy using Chi-squared test. As there were patients with repeat studies, analysis was performed for both initial and final exam results. Same dataset was used for initial and final exams in patients with only one exam. RESULTS: Out of 138 patients, 15 patients underwent decompressive craniectomy (11%) and 123 patients were managed medically (89%). On the initial exam, negative brain flow was demonstrated in 11 of 15 patients with craniectomy (73.3%) and 106 of 123 patients without craniectomy (86.2%). On the final exam, negative brain flow was demonstrated 12 of 15 patients with craniectomy (80%) and 111 of 123 patients without craniectomy (90.2%). There were no statistically significant differences between the two groups on both initial and final exams (p = 0.19 and 0.23, respectively). CONCLUSION: In patients with suspected brain death, history of decompressive craniectomy does not affect the result of brain perfusion scintigraphy.

Boron: the essential element for vascular plants that never was.

Although a requirement for boron is a well-established feature of vascular plants, its designation, for almost a century, as essential is challenged and, instead, the proposal is made that it has never been so as conventionally defined. This is because an alternative interpretation of published evidence negates its compliance with one of the criteria for essentiality, that its effects are direct. The alternative, here postulated, is that boron is, and always has been, potentially toxic, a feature which, for normal growth, development and reproduction, needed to be nullified. This was enabled by exploitation of boron's ability to be chemically bound to compounds with cis-hydroxyl groups. Although particular cell wall carbohydrate polymers, glycoproteins and membrane glycolipids are among candidates for this role, it is here proposed that soluble phenolic metabolites of, or related to, the components of the pathway of lignin biosynthesis, themselves potentially toxic, are primarily used by vascular plants. When metabolic circumstances allow these phenolics to accumulate endogenously in the cytoplasm, their own inherent toxicity is also alleviated, partially at least, by formation of complexes with boron. This chemical reciprocity, enhanced by physical sequestration of the complexes in vacuoles and/or apoplast, thus achieves, in a flexible but indirect manner, a minimization of the inherent toxicities of both boron and relevant phenolics. In these ways, the multifarious outcomes of impairments, natural or experimental, to this interplay are responsible for the lack of consensus to explain the diverse effects observed in the many searches for boron's primary metabolic role, here considered to be nonexistent. In particular, since a toxic element cannot have 'deficiency symptoms', those previously so-called are postulated to be largely due to the expressed toxicity of phenylpropanoids. A principal requirement for the otherwise toxic boron is to nullify, by means of its indirect chemical and physical sequestration, such expression. In these ways, it is therefore neither an essential nor a beneficial element as currently strictly defined.

Insights into carotenoid accumulation using VIGS to block different steps of carotenoid biosynthesis in petals of California poppy.

KEY MESSAGE: Viral-induced gene silencing of selected biosynthetic genes decreased overall carotenoid accumulation in California poppy. Regulation of carotenogenesis was linked with pigment sequestration, not changes in biosynthetic gene expression. Genes of carotenogenesis are well described, but understanding how they affect carotenoid accumulation has proven difficult because of plant lethality when the pigments are lacking. Here, we used a Tobacco Rattle Virus-based virus-induced-gene-silencing (VIGS) approach in California poppy (Eschscholzia californica) to investigate how silencing of the carotenoid biosynthetic pathway genes affects carotenoid metabolite accumulation and RNA transcript abundance of the carotenoid biosynthetic pathway genes. VIGS of upstream (PDS and ZDS) and downstream (ßOH and ZEP) genes reduced transcript abundance of the targeted genes in the poppy petals while having no effect on abundance of the other carotenogenesis genes. Silencing of PDS, ZDS, ßOH and ZEP genes reduced total pigment concentration by 75-90% and altered petal colour. HPLC and LC-MS measurements suggested that petal colour changes were caused by substantially altered pigment profiles and quantity. Carotenoid metabolites were different to those normally detected in wild-type petals accumulated but overall carotenoid concentration was less, suggesting the chemical form of carotenoid was important for whether it could be stored at high amounts. In poppy petals, eschscholtzxanthin and retro-carotene-triol were the predominant carotenoids, present mainly as esters. Specific esterification enzymes for specific carotenoids and/or fatty acids appear key for enabling petal carotenoids to accumulate to high amounts. Our findings argue against a direct role for carotenoid metabolites regulating carotenogenesis genes in the petals of California poppy as transcript abundance of carotenogenesis genes studied was unchanged, while the petal carotenoid metabolite profile changed substantially.

Hepatotoxic Dose Thresholds by Positron-Emission Tomography After Yttrium-90 Radioembolization of Liver Tumors: A Prospective Single-Arm Observational Study.

PURPOSE: To define a threshold radiation dose to non-tumoral liver from 90Y radioembolization that results in hepatic toxicity using pair-production PET. MATERIALS AND METHODS: This prospective single-arm study enrolled 35 patients undergoing radioembolization. A total of 34 patients (27 with HCC and 7 with liver metastases) were included in the final analysis. Of 27 patients with underlying cirrhosis, 22 and 5 patients were Child-Pugh A and B, respectively. Glass and resin microspheres were used in 32 (94%) and 2 (6%) patients, respectively. Lobar and segmental treatment was done in 26 (76%) and 8 (24%) patients, respectively. Volumetric analysis was performed on post-radioembolization time-of-flight PET imaging to determine non-tumoral parenchymal dose. Hepatic toxicity was evaluated up to 120 days post-treatment, with CTCAE grade ≤ 1 compared to grade ≥ 2. RESULTS: The median dose delivered to the non-tumoral liver in the treated lobe was 49 Gy (range 0-133). A total of 15 patients had grade ≤ 1 hepatic toxicity, and 19 patients had grade ≥ 2 toxicity. Patients with a grade ≥ 2 change in composite toxicity (70.7 vs. 43.8 Gy), bilirubin (74.1 vs. 43.3 Gy), albumin (84.2 vs. 43.8 Gy), and AST (94.5 vs. 47.1 Gy) have significantly higher non-tumoral parenchymal doses than those with grade ≤ 1. Liver parenchymal dose and Child-Pugh status predicted grade ≥ 2 toxicity, observed above a dose threshold of 54 Gy. CONCLUSION: Increasing delivered 90Y dose to non-tumoral liver measured by internal pair-production PET correlates with post-treatment hepatic toxicity. The likelihood of toxicity exceeds 50% at a dose threshold of 54 Gy. ClinicalTrials.gov identifier: NCT02848638.

Prospective Trial Using Internal Pair-Production Positron Emission Tomography to Establish the Yttrium-90 Radioembolization Dose Required for Response of Hepatocellular Carcinoma.

PURPOSE: To prospectively assess the threshold dose for objective response of hepatocellular carcinoma (HCC), using 90Y internal pair-production positron emission tomography (PET) to quantify the radiation dose delivered to hepatic tumors after radioembolization. METHODS AND MATERIALS: A prospective study was performed under institutional review board approval from 2012 to 2014. Thirty-five patients with primary and secondary liver tumors undergoing 90Y treatment were recruited. Eight patients did not meet inclusion criteria, and 27 patients with HCC were included for analysis. Time-of-flight PET imaging was performed immediately after radioembolization and voxel values converted into 90Y activity. The radioembolization dose was calculated from PET images, and image segmentation was performed with volumetric analysis of dose deposition within tumors. Radiographic response was assessed on follow-up imaging. RESULTS: Treated HCC showed 84% objective response, 11% stable disease, and 5% progressive disease according to modified RECIST 1.1 response criteria. Responders had a higher median 90Y tumor dose than nonresponders (225 Gy vs 83 Gy, P < .01). Logistic regression models show tumor dose (P = .002) strongly predicted objective response. All nonresponders had tumor dose <200 Gy. No statistical difference for patient age, tumor volume, multifocal or extrahepatic disease, portal vein invasion, or injected 90Y activity was found between responders and nonresponders. CONCLUSIONS: Hepatocellular carcinoma that resulted in objective response after radioembolization had a greater median tumor dose of 225 Gy, compared with 83 Gy in nonresponders. Delivered tumor dose can be assessed by PET and significantly impacts treatment response in HCC.

I-131 uptake in fat necrosis of the breast.

I-131 uptake in the breast has been described with a variety of normal and pathologic conditions. We present the case of a 38-year-old female who received 317 millicuries of radioactive I-131 treatment for papillary thyroid carcinoma. Post-treatment scan demonstrated I-131 uptake in an area of fat necrosis in the breast.

Spontaneous Intracranial Hypotension With Site of Leak Detected Only After 111In-DTPA Cisternogram.

A 54-year-old man with a 3-week history of orthostatic headache and acute on chronic subdural hematoma presented with imaging findings suggestive of spontaneous intracranial hypotension. Three myelograms were negative for leak, and nontargeted epidural blood patches did not result in symptom relief. A cerebrospinal fluid leak study using In-DTPA with SPECT/CT demonstrated a focal area of asymmetric activity at the left C2 nerve root. A left C2 root tie-off, targeted epidural blood patch, and Dura seal glue resulted in resolution of patient symptomatology highlighting the importance of fused SPECT/CT images in detection of an occult cerebral spinal fluid leak.

Advances in PET Imaging of Degenerative, Cerebrovascular, and Traumatic Causes of Dementia.

In this review we present the most recent advances in nuclear medicine imaging as a diagnostic and management tool for dementia. The clinical diagnosis of dementia syndromes can be challenging for physicians, particularly in the early stages of disease. Given the growing number of individuals affected by dementia, early and accurate diagnosis can lead to improved clinical management of patients. Although tests are available for exclusion of certain causes of cognitive impairment, the results rarely allow the clinician to make a definitive diagnosis. For this reason, information obtained from imaging ("imaging biomarkers") is playing an increasingly important role in the workup of patients with suspected dementia. Imaging biomarkers also provide indispensable tools for clinical and preclinical studies of dementing illnesses to elucidate their pathophysiology and to develop better therapies. A wide range of imaging has been used to diagnose and investigate neurodegenerative disorders including structural, cerebral perfusion, glucose metabolism, neurochemical, and molecular imaging. In the first section, we discuss the imaging methods used in clinical practice to diagnose dementia as well as explore additional experimental modalities that are currently used as research tools. In the second section, a comprehensive review covering the myriad aspects of vascular disease as a cause of dementia is presented and illustrated with MRI- and PET-focused case examples. In the third section, advances in imaging Alzheimer disease pathology are emphasized by reviewing current approaches for PET imaging with ß-amyloid imaging agents. We provide an outline for the appropriate use criteria for ß-amyloid imaging agents in dementia. In addition, the recognition of the importance of neocortical neurofibrillary tangles as related to Alzheimer disease progression has led to the development of promising tau imaging agents such as [(18)F]T807. The last section provides a history brain trauma as a cause of chronic traumatic encephalopathy. Although the recognition of cognitive deficits from brain trauma dates back to the early part of last century, recent advances in our understanding of the neurobiology has led to the hope of developing molecular imaging methods for earlier diagnoses and treatment. This has become increasingly important given the raised public and physician awareness of the high incidence of this pathology in military conflicts and sports-related injuries. Overall advancements in nuclear medicine imaging have led to an improvement in the detection and accurate identification of dementia and its underlying causes. With both primary and secondary causes of dementia demonstrating often overlapping presentations, nuclear medicine imaging can play a key role not only in the diagnosis but the understanding of dementia. With earlier diagnosis and better understanding comes the hope of improved treatments or possibly someday a cure.

Characterisation of betalain biosynthesis in Parakeelya flowers identifies the key biosynthetic gene DOD as belonging to an expanded LigB gene family that is conserved in betalain-producing species.

Plant betalain pigments are intriguing because they are restricted to the Caryophyllales and are mutually exclusive with the more common anthocyanins. However, betalain biosynthesis is poorly understood compared to that of anthocyanins. In this study, betalain production and betalain-related genes were characterized in Parakeelya mirabilis (Montiaceae). RT-PCR and transcriptomics identified three sequences related to the key biosynthetic enzyme Dopa 4,5-dioxgenase (DOD). In addition to a LigB gene similar to that of non-Caryophyllales species (Class I genes), two other P. mirabilis LigB genes were found (DOD and DOD-like, termed Class II). PmDOD and PmDOD-like had 70% amino acid identity. Only PmDOD was implicated in betalain synthesis based on transient assays of enzyme activity and correlation of transcript abundance to spatio-temporal betalain accumulation. The role of PmDOD-like remains unknown. The striking pigment patterning of the flowers was due to distinct zones of red betacyanin and yellow betaxanthin production. The major betacyanin was the unglycosylated betanidin rather than the commonly found glycosides, an occurrence for which there are a few previous reports. The white petal zones lacked pigment but had DOD activity suggesting alternate regulation of the pathway in this tissue. DOD and DOD-like sequences were also identified in other betalain-producing species but not in examples of anthocyanin-producing Caryophyllales or non-Caryophyllales species. A Class I LigB sequence from the anthocyanin-producing Caryophyllaceae species Dianthus superbus and two DOD-like sequences from the Amaranthaceae species Beta vulgaris and Ptilotus spp. did not show DOD activity in the transient assay. The additional sequences suggests that DOD is part of a larger LigB gene family in betalain-producing Caryophyllales taxa, and the tandem genomic arrangement of two of the three B. vulgaris LigB genes suggests the involvement of duplication in the gene family evolution.

Regreening in spathes of Zantedeschia after anthesis: its physiology and control by fructification and hormones.

The mature pigmented spathe of Zantedeschia is characterized by a developmental process, wherein the spathe regreens after anthesis and prior to senescence of the inflorescence. Previous research has shown that spathe regreening involves redifferentiation of chloroplasts and re-accumulation of chlorophyll, but the detailed physiological changes associated with regreening are still largely unknown. Using Zantedeschia aethiopica and the Zantedeschia pentlandii variety 'Best Gold' as models, this study explores the physiological mechanism and possible roles of fructification, 6-benzylaminopurine (BAP) and gibberellin (GA3 ) in induction or progression of spathe regreening. Application of BAP stimulated regreening in spathe tissue of 'Best Gold' by enhancing accumulation of carotenoid and chlorophyll, and also increasing stacking of grana. In contrast, GA3 retarded formation of double-membrane lamella during chloroplast redifferentiation, thus delaying the onset of regreening. We suggest that these actions of BAP and GA3 have a synergistic effect in delaying the onset of regreening in 'Best Gold' so that when applied together retardation of chlorophyll accumulation, chloroplast redifferentiation and accumulation of carotenoids were enhanced. The elimination of fructification did not prevent the occurrence of regreening in either Zantedeschia model plants, indicating that fructification was not a prerequisite for the induction of regreening. It is still unclear how regreening in Zantedeschia is triggered. We propose that the onset of regreening in Zantedeschia is likely to be a genetically programmed event.

Differential alterations of dopamine transporter in the striatum and midbrain in patients with parkinsonian syndrome.

OBJECTIVES: Differential vulnerabilities of subregional dopamine neurons have been suggested in movement disorders such as idiopathic Parkinson disease. In this study, we examined dopamine transporter (DaT) density in the striatum versus midbrain (MB) in patients with nigrostriatal denervation. METHODS: Brain SPECT was performed in 39 patients with parkinsonian syndrome (age 61 ± 15 years, 18 male patients) 4 hours after IV injection of 3 to 5 mCi 123I ioflupane using SPECT-CT acquisition. Images were reconstructed using OSEM with resolution recovery and correction for scatter and attenuation based on a low-dose CT. Peak pixel counts within the caudate head (CA), mid putamen (PT), and MB localized by sagittal CT, as well as averaged counts around the calcarine fissure as reference, were determined by region-of-interest analysis. Semiquantitative DaT values were expressed as CA, PT, or MB uptake relative to the reference. We then assessed the relationship between the MB measurements and independent clinical evaluation of motor symptoms in these patients. RESULTS: Averaged striatal DaT values for both hemispheres ranged from 1.67 to 6.59 for CA, 1.50 to 5.33 for PT, and 1.08 to 2.24 for MB. Within the high striatal DaT group (mean, 4.76 [SD, 0.55]) and low DaT group (mean, 2.71 [SD, 0.58]; dichotomy defined as a threshold of 4), mean DaT values in MB were 1.68 (SD, 0.32) and 1.53 (SD, 0.29), respectively, indicating nonsignificant 9% decrease (P > 0.15) in comparison to 43% decrease in the averaged striatal uptake. Within the high striatal DaT group, Pearson correlations between DaT values of CA and PT versus MB were highly significant at 0.81 and 0.82 (P ≤ 0.001), respectively, but those correlations were not significant, 0.35 (P > 0.05) and 0.06 (P > 0.75), in the low striatal DaT group. Midbrain uptake measurements did not correlate with motor symptoms (bradykinesia, tremor, rigidity, and postural instability). CONCLUSIONS: These findings indicate that reductions in DaT values in the striatum and MB are not necessarily simultaneous with the process of nigrostriatal denervation, and correlation of DaT values among CA/PT and MB becomes weaker as the denervation becomes more severe. Differential regional DaT loss may indicate differential vulnerability of DaT-containing neurons in these structures or could be in part related to tracer binding to non-DaT targets.