Changes in apparent diffusion coefficients of metabolites in rat brain after middle cerebral artery occlusion measured by proton magnetic resonance spectroscopy.

Diffusion-weighted proton MR spectroscopy and imaging have been applied to a rat brain model of unilateral middle cerebral artery occlusion between 1 and 4 hr post occlusion. Similar apparent diffusion coefficients (ADC) of most metabolites were observed within each hemisphere. In the ischemic ipsilateral hemisphere, the ADCs were (0.083--0.116). 10(-3) mm(2)/sec for lactate (Lac), alanine (Ala), gamma-amino butyric acid (GABA), N-acetyl aspartate (NAA), glutamine (Gln), glutamate (Glu), total creatine (tCr), choline-containing compounds (Cho), and myo-inositol (Ins), in the contralateral hemisphere (0.138--0.158). 10(-3) mm(2)/sec for NAA, Glu, tCr, Cho, and Ins. Higher ADCs was determined for taurine (Tau) in the ipsilateral (0.144. 10(-3) mm(2)/sec) and contralateral (0.198. 10(-3) mm(2)/sec) hemisphere. In the ischemic hemisphere, a relative ADC decrease to 65--75% was observed for NAA, Glu, tCr, Cho, Ins and Tau, which was similar to the decrease of the water ADC (to 67%). The results suggest a common cause of the observed ADC changes and provide a broader experimental basis to evaluate theories of water and metabolite diffusion. Magn Reson Med 45:383-389, 2001.     

6-羟基多巴胺诱发帕金森病大鼠模型的制作和评价

目的 向大鼠中脑黑质区注入6-羟基多巴胺(6-OHDA)建立帕金森病(PD)大鼠模型,并从行为学(ethology)及组织病理、生化角度对该模型进行评价.方法 将6-OHDA立体定向微量注入大鼠右侧中脑黑质(SN)区,观察阿朴吗啡(APO)诱发的大鼠旋转行为及黑质细胞形态学变化,测定脑组织液中儿茶酚胺类物质含量及黑质酪氨酸羟化酶的免疫活性.结果 120只大鼠中经APO诱导后有67只(占55.8%)持续转向健侧(旋转圈数＞7r/min),帕金森病大鼠模型复制成功.PD鼠注射侧黑质区多巴胺能神经元数量较对侧明显减少,体积缩小,结构欠清晰.注射侧脑组织液中多巴胺(DA)、3,4-二羟基苯酸(DOPAC)、高香草酸(HVA)、5-羟色胺(5-HT)含量均低于对侧,注射侧黑质致密部酪氨酸羟化酶(TH)免疫阳性细胞较健侧明显减少.连续观察10个月,PD模型大鼠的异常旋转行为无自发性恢复.结论 用6-OHDA选择性损毁大鼠黑质多巴胺能神经元,可造成与PD患者相似的基本病理变化,建立起可靠而稳定的PD大鼠模型.     

Manganese-enhanced MRI in a rat model of Parkinson's disease

PURPOSE: To measure intra- and inter-hemispheric connectivity within the basal ganglia (BG) nuclei in healthy and in unilateral 6-hydroxydopamine (6-OHDA) Parkinson disease rat model in order to test the BG interhemispheric connectivity hypothesis. MATERIAL AND METHODS: The manganese-enhanced MRI (MEMRI) method with direct injection of manganese chloride into the entopeduncular (EP), substantia nigra (SN), and the Habenula nuclei in unilateral 6-OHDA (N = 22) and sham-operated (N = 16) rat groups was used. MEMRI measurements were applied before, 3, 24, and 48 hours post-manganese injection. Signal enhancements in T1-weighted images were compared between groups. RESULTS: Manganese injection into the EP nucleus resulted with bihemispheric signal enhancements in the habenular complex (Hab) at both groups with stronger enhancements in the 6-OHDA group. It also exhibited lower sensorimotor cortex signal enhancement in the 6-OHDA rat group. SN manganese injection caused enhanced anteroventral thalamic and habenular nuclei signals in the 6-OHDA rat group. Manganese habenula injection revealed enhanced interpeduncular (IP) and raphe nuclei signals of the 6-OHDA rat group. CONCLUSION: Modulations in the effective intra- and interhemispheric BG connectivity in unilateral 6-OHDA Parkinson's disease (PD) rat model support the BG interhemispheric connectivity hypothesis and suggest a linkage between the dopaminergic and serotonergic systems in PD, in line with clinical symptoms.     

MR定量磁化率成像在帕金森病临床诊断中的价值研究

目的 分析帕金森病（PD）患者的中脑黑质及红核的磁化率变化情况,明确MR定量磁化率成像（QSM）技术在PD临床诊断中的价值。 方法 回顾性分析2017年2月至2019年8月于佛山市第一人民医院诊断为PD的患者39例（PD组）,其中男性17例、女性22例,年龄47~80（65.44±9.78）岁。根据改良Hoehn-Yahr分级将患者分为早期PD组（23例）及中晚期PD组（16例）,另选取20名健康体检者作为正常对照组。所有患者及正常对照者均进行QSM扫描,测量各组中脑左右两侧黑质和红核的磁化率,取平均值。采用独立样本t检验分析PD患者的中脑黑质及红核磁化率的变化特征,并与PD的临床诊断、分级和病程进行Pearson相关性分析;采用单因素分析中脑左右侧黑质及红核的磁化率变化与临床肢体运动障碍症状侧的关系。 结果 PD组的中脑黑质及红核的磁化率较正常对照组显著升高 [（0.073±0.017）×10?3对（0.058±0.028）×10?3,t=?2.125,P=0.043;（0.094±0.020）×10?3对（0.072±0.035）×10?3,t=?2.605,P=0.015]。PD组的中脑黑质及红核的磁化率与Hoehn-Yahr分级无显著相关性（r=0.051,P=0.759;r=0.045,P=0.788）;黑质的磁化率与病程呈显著正相关（r=0.420,P=0.008）,红核的磁化率与病程无相关性（r=0.241,P=0.130）。PD组的中脑左右侧黑质、红核的磁化率变化与患者临床发病时肢体运动障碍症状的表现无显著相关性（黑质:F_左=0.661,P_左=0.421;F_右=1.153,P_右=0.290。红核:F_左=0.006,P_左=0.940;F_右=0.109,P_右=0.743）。 结论 QSM技术能够测量中脑黑质及红核的磁化率,并间接反映脑内铁沉积情况,对PD诊断及病程评估具有临床价值。     

Transcranial parenchymal sonography in the diagnosis of Parkinson's disease

BACKGROUND/AIM: Modem ultrasound systems allow high-resolution transcranial sonography (TCS) of the brain structures. Enlargement of the echogenic signal (hyperechogenicity) of the substantia nigra (SN) has been reported as a highly characteristic finding in idiopathic Parkinson's disease (PD) and is thought to reflect increased amounts of iron, bound to proteins other than ferritin, in the SN in the course of neurodegeneration. The aim of our study was to investigate the prevalence of the SN hyperechogenicity in PD patients, as well as its possible clinical correlates. METHODS: The study comprised 103 consecutive PD patients and 50 healthy age-matched controls. For TCS examination a colour-coded, phased array ultrasound system equipped with a 2.5 MHz transducer was used (ESAOTE Technos MP, Italia). The examination was performed through a preauricular acoustic bone window with a penetration depth of 16 cm and a dynamic range of 45-50 dB. The SN was identified within the butterfly shaped structure of the mesencephalic brainstem, with scanning from both temporal windows. RESULTS: The SN hyperechogenicity was identified in 95 out of 103 examined PD patients (92%), which was marked in 60 (63%), and moderate in 35 patients (37%). Median SN echogenic size was larger contralateral to the clinically more affected side of the body. Unilateral SN hyperechogenicity was also found in 5 out of 50 healthy controls (10%). No ventricular enlargements were notified in our study. CONCLUSION: Our study demonstrated SN hyperechogenicity in more than 90% of PD patients. In adult subjects without neurological symptoms, the TCS finding of at least unilaterally marked SN hyperechogenicity indicates a subclinical functional impairment of the nigrostriatal dopaminergic system.     

In vivo detection of cortical GABA turnover from intravenously infused [1-13C]D-glucose.

In this study [2-(13)C] gamma-aminobutyric acid (GABA) was spectrally resolved in vivo and detected simultaneously with [4-(13)C]glutamate (Glu) and [4-(13)C]glutamine (Gln) in the proton spectra obtained from a localized 40 microL voxel in rat neocortex with the use of an adiabatic (1)H-observed, (13)C-edited (POCE) spectroscopy method and an 89-mm-bore vertical 11.7 Tesla microimager. The time-resolved kinetics of (13)C label incorporation from intravenously infused [1-(13)C]glucose into [4-(13)C]Glu, [4-(13)C]Gln, and [2-(13)C]GABA were measured after acute administration of gabaculine, a potent and specific inhibitor of GABA-transaminase. In contrast to previous observations of a rapid turnover of [2-(13)C]GABA from [1-(13)C]glucose in intact rat brain, the rate of (13)C incorporation from [1-(13)C]glucose into [2-(13)C]GABA in the gabaculine-treated rats was found to be significantly reduced as a result of the blockade of the GABA shunt.     

Quantitative proton spectroscopic imaging of the neurochemical profile in rat brain with microliter resolution at ultra-short echo times.

Proton spectroscopy allows the simultaneous quantification of a high number of metabolite concentrations termed the neurochemical profile. The spin echo full intensity acquired localization (SPECIAL) scheme with an echo time of 2.7 ms was used at 9.4T for excitation of a slab parallel to a home-built quadrature surface coil in conjunction with phase encoding in the two remaining spatial dimensions to yield an effective spatial resolution of 1.7 microL. The absolute concentrations of at least 10 metabolites were calculated from the spectra of individual voxels using LCModel analysis. The calculated concentrations were used for constructing quantitative metabolic maps of the neurochemical profile in normal and pathological rat brain. Summation of individual spectra was used to assess the neurochemical profile of unique brain regions, such as corpus callosum, in rat for the first time. Following focal ischemia in rat pups, imaging the neurochemical profile indicated increased choline groups in the ischemic core and increased glutamine in the penumbra, which is proposed to reflect glutamate excitotoxicity. We conclude that it is feasible to achieve a sensitivity that is sufficient for quantitative mapping of the neurochemical profile at microliter spatial resolution.     

Localized short-echo-time proton MR spectroscopy with full signal-intensity acquisition.

We developed a short-echo-time (TE) sequence for proton localized spectroscopy by combining a 1D add-subtract scheme with a doubly slice-selective spin-echo (SE) sequence. The sequence preserves the full magnetization available from the selected volume of interest (VOI). By reducing the number of radiofrequency (RF) pulses acting on transverse magnetization, we were able to minimize the TE to the level that is achievable with the stimulated echo acquisition mode (STEAM) technique, and also gained a twofold increase in sensitivity. The use of an adiabatic pulse in the add-subtract localization improved the efficiency of excitation in spatially inhomogeneous RF fields, which are frequently encountered at high magnetic fields. The localization performance and sensitivity gains of this method, which is termed SPin ECho, full Intensity Acquired Localized (SPECIAL) spectroscopy, were demonstrated in vivo in rat brains. In conjunction with spectroscopic imaging, a 2-microl spatial resolution was accomplished with a signal-to-noise ratio (SNR) above 30, which is usually sufficient for reliable quantification of a large number of metabolites (neurochemical profile).     

Examining alterations in GABA concentrations in the basal ganglia of patients with Parkinson’s disease using MEGA-PRESS MRS

Purpose

The aim of this study was to compare the gamma-amino butyric acid (GABA) levels in the left basal ganglia (BG) of patients with Parkinson’s disease (PD) to those of healthy control (HC) volunteers using proton magnetic resonance spectroscopy (¹H MRS).

Materials and methods

The GABA+ signal—the composite signal from GABA, macromolecules (MMs), and homocarnosine—was detected. GABA+ levels were examined in 21 PD patients and 15 age- and sex-matched HCs. 3T-¹H-MRS using the Mescher–Garwood point-resolved spectroscopy (MEGA-PRESS) sequence was performed in order to detect GABA+ levels in the left BG, and the spectra were processed using the Gannet software. Differences in GABA+ levels between the two groups were analyzed using independent t-test analysis.

Results

The GABA+ levels were significantly lower (P < 0.001) in the left BG of the patients with PD (1.31 ± 0.21 i.u.) than in the left BG of the HCs (1.62 ± 0.26 i.u.).

Conclusion

The lower GABA+ levels in the left BG of the PD patients suggest that GABA plays an important role in the pathogenesis of PD. The reduced GABA+ levels in the PD patients may be associated with GABAergic dysfunction.

     

Nitric oxide amplifies the excitatory to inhibitory neurotransmitter imbalance accelerating oxygen seizures.

CNS O2 toxicity is manifested most profoundly by generalized motor convulsions. The hypothesis was tested that HBO2 triggers seizures by an excitatory to inhibitory neurotransmitter imbalance produced by neuronal nitric oxide (NO) activity. Anesthetized rats were exposed to 5 ATA HBO2 for 75 min with or without prior inhibition of nNOS. Interstitial NO and amino acids: aspartate (Asp), glutamate (Glu) and gamma-aminobutyric acid (GABA) were determined in the striatum by microdialysis coupled with HPLC. Blood flow and EEG in the same striatal region were measured simultaneously. Rats treated with 7-NI showed no EEG spikes of O2 toxicity, while seizure latency for untreated rats was 63 +/- 7 min. Significant increases in NO metabolites and blood flow were observed in control rats before seizures. HBO2 did not change Glu significantly and increased Asp slightly whereas GABA decreased progressively by 37 +/- 7%. Pretreatment with 7-NI led to a significantly smaller decline in GABA. Overall, the simplified excitotoxicity index Glu/GABA increased significantly after 60 min of HBO2 in control but fell in rats treated with 7-NI. We conclude that HBO2-stimulated neuronal NO production promotes an imbalance between glutamatergic and GABAergic synaptic function implicated in the genesis of oxygen-induced seizures.     

力竭运动前后活体大鼠纹状体谷氨酸和γ-氨基丁酸水平的动态变化

目的:观察一次性力竭运动过程中大鼠纹状体内神经递质谷氨酸(Glu)和γ-氨基丁酸(GABA)含量及其比值的动态变化,探讨运动疲劳后纹状体神经元电活动改变的可能机制.方法:8周龄雄性Wistar大鼠8只,通过手术预先将透析套管定植入左侧纹状体(P:0.2,L:3,H:3.2).采用活体微透析与高效液相色谱(HPLC)检测...     

6-羟基多巴脑内注射建立帕金森病大鼠模型的实验研究

目的 探讨6-羟基多巴脑内注射建立稳定的帕金森病大鼠模型的方法.方法 将6-羟基多巴立体定向注入大鼠右侧前脑内侧束和中脑被盖腹侧区,观察大鼠的行为变化和中脑黑质区的形态学变化.结果 注药后2周,动物经阿扑吗啡诱导即出现向健侧的旋转行为,注射效果稳定.在长达3个月的观察中,动物的旋转行为稳定,无明显的差异.形态学显示,毁损侧的黑质致密部和中脑被盖腰侧区的酪氨酸羟化酶阳性神经元的数量明显减少.结论 通过6-羟基多巴脑内注射的方法可以建立起稳定、有效的帕金森病大鼠模型.     

Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS.

In vivo MR spectroscopy (MRS) studies have shown reductions in NAA/Cr levels in patients with severe neurocognitive deficits due to AIDS dementia complex (ADC), also known as neuroAIDS. The relationship between the cellular changes within the brain during neuroAIDS and the role of NAA/Cr as a metabolic marker remains unclear. In order to clarify the relationship between NAA/Cr and disease severity we utilized the simian immunodeficiency virus (SIV)/macaque model of encephalitis. High-field proton MRS was performed on extracted metabolites from frontal cortex tissue samples of 29 rhesus macaques (6 healthy, 23 moribund with AIDS). Neuropathologic determination of encephalitis severity for each animal was completed and was found to correlate with NAA/Cr levels. Decreases in Glu/Cr and GABA/Cr may indicate that both excitatory and inhibitory neurons are affected. Highly significant correlations between NAA/Cr, Glu/Cr, and GABA/Cr were observed. These neuronal metabolites were also decreased in the absence of classical SIV encephalitis (SIVE). At any disease classification, animals inoculated with SIVmac251 were found to have lower levels of NAA/Cr than animals inoculated with SIVmac239. In considering therapy for neuroAIDS the findings here support prevention of the encephalitic process, but suggest that suppressing the formation of multinucleated giant cells alone would be insufficient to prevent neuronal injury.     

SWI 测量脑铁在帕金森病病情评估中的应用价值

目的：探讨磁敏感加权成像(SWI)测量脑铁在帕金森病(PD)的诊断以及病情评估中的应用价值。方法30例经临床诊断为PD 的患者行颅脑磁共振常规序列和 SWI 序列扫描,PD 患者病情评估采用统一帕金森病评定量表(UPDRS)。在 SWI 序列相位图上手动测量患者黑质、红核、尾状核、苍白球和壳核的相位值,分析以上感兴趣区(ROI)核团的相位值与 UPDRS 评分的相关性。结果ROI 核团病重侧与病轻侧的相位值比较无差异(黑质,P =0.120;红核,P =0.402;尾状核,P =0.196;苍白球,P =0.616;壳核, P =0.985);PD 患者 UPDRS Ⅲ评分分别与黑质、尾状核和苍白球的相位值呈负相关(黑质-UPDRS Ⅲ：r =-0.407,P =0.026;尾状核-UPDRS Ⅲ：r=-0.424,P=0.02;苍白球-UPDRS Ⅲ：r=-0.363,P=0.048);黑质相位值与 UPDRS Ⅴ的分期呈负相关(r=-0.373, P =0.043);尾状核相位值与 UPDRSⅠ的评分呈负相关(r=-0.367,P =0.046);苍白球相位值与 UPDRS Ⅲ中的步态障碍评分呈负相关(r=-0.411,P =0.024),而其余核团的相位值与 UPDRS 评分不相关。结论SWI 可以定量评估 PD 患者脑部核团的异常铁沉积,为 PD 的临床诊断和病情评估提供参考。     

Proton echo-planar spectroscopic imaging of J-coupled resonances in human brain at 3 and 4 Tesla.

In this multicenter study, 2D spatial mapping of J-coupled resonances at 3T and 4T was performed using short-TE (15 ms) proton echo-planar spectroscopic imaging (PEPSI). Water-suppressed (WS) data were acquired in 8.5 min with 1-cm(3) spatial resolution from a supraventricular axial slice. Optimized outer volume suppression (OVS) enabled mapping in close proximity to peripheral scalp regions. Constrained spectral fitting in reference to a non-WS (NWS) scan was performed with LCModel using correction for relaxation attenuation and partial-volume effects. The concentrations of total choline (tCho), creatine + phosphocreatine (Cr+PCr), glutamate (Glu), glutamate + glutamine (Glu+Gln), myo-inositol (Ins), NAA, NAA+NAAG, and two macromolecular resonances at 0.9 and 2.0 ppm were mapped with mean Cramer-Rao lower bounds (CRLBs) between 6% and 18% and approximately 150-cm(3) sensitive volumes. Aspartate, GABA, glutamine (Gln), glutathione (GSH), phosphoethanolamine (PE), and macromolecules (MMs) at 1.2 ppm were also mapped, although with larger mean CRLBs between 30% and 44%. The CRLBs at 4T were 19% lower on average as compared to 3T, consistent with a higher signal-to-noise ratio (SNR) and increased spectral resolution. Metabolite concentrations were in the ranges reported in previous studies. Glu concentration was significantly higher in gray matter (GM) compared to white matter (WM), as anticipated. The short acquisition time makes this methodology suitable for clinical studies.     

X线照射对实验性癫痫大鼠脑皮层氨基酸递质含量的影响

目的 探讨癫痫大鼠放射治疗的作用机制与时间、合理剂量。方法 利用慢性点燃癫痫大鼠进行24、12、6、0Gy的X线照射，用氨基酸分析仪测定不同照射剂量癫痫大鼠及照射后1h、24h、1周时癫痫大鼠额叶皮层内的主要兴奋性与抑制性氨基酸递质含量变化。结果 X线放射治疗后发生变化的氨基酸递质主要是G1u与GABA，与对照组(0Gy)比较，12Gy、24Gy组Glu含量降低，GABA含量升高，Glu／GABA值降低；照射后1h、24h、1周后GABA含量升高，Glu／GABA值降低，其中以24h比值下降最为明显。结论 放射治疗癫痫的机制主要是GABA与Glu递质发生快速而持续的变化；癫痫大鼠接受12Gy的放射治疗较为合理。     

MR spectroscopy of the human brain with enhanced signal intensity at ultrashort echo times on a clinical platform at 3T and 7T

Recently, the spin‐echo full‐intensity acquired localized (SPECIAL) spectroscopy technique was proposed to unite the advantages of short TEs on the order of milliseconds (ms) with full sensitivity and applied to in vivo rat brain. In the present study, SPECIAL was adapted and optimized for use on a clinical platform at 3T and 7T by combining interleaved water suppression (WS) and outer volume saturation (OVS), optimized sequence timing, and improved shimming using FASTMAP. High‐quality single voxel spectra of human brain were acquired at TEs below or equal to 6 ms on a clinical 3T and 7T system for six volunteers. Narrow linewidths (6.6 ± 0.6 Hz at 3T and 12.1 ± 1.0 Hz at 7T for water) and the high signal‐to‐noise ratio (SNR) of the artifact‐free spectra enabled the quantification of a neurochemical profile consisting of 18 metabolites with Cramér‐Rao lower bounds (CRLBs) below 20% at both field strengths. The enhanced sensitivity and increased spectral resolution at 7T compared to 3T allowed a two‐fold reduction in scan time, an increased precision of quantification for 12 metabolites, and the additional quantification of lactate with CRLB below 20%. Improved sensitivity at 7T was also demonstrated by a 1.7‐fold increase in average SNR (= peak height/root mean square [RMS]‐of‐noise) per unit‐time. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

雌激素对PD模型大鼠黑质纹状体通路的保护作用及其机制探讨

目的研究雌激素（Estrogen）对6-羟基多巴（6-OHDA）制备的去卵巢（OVX）帕金森病（PD）模型大鼠黑质纹状体通路的保护作用及其可能机制。方法应用6-OHDA两点注射单侧损毁内侧前脑束（MFB）制备OVXPD模型大鼠,侧脑室给予17-β雌二醇（17-βestradiol,1μg/5μl）,观察大鼠旋转行为、黑质酪氨酸羟化酶（TH）基因表达、黑质铁染色阳性细胞数量和纹状体内多巴胺（DA）及其代谢产物含量的变化。结果雌激素用药组可明显减少阿朴吗啡诱导的PD模型大鼠单侧旋转行为（P〈0.01）。在损毁侧黑质,雌激素用药组TH基因的表达较PD模型组明显增加（P〈0.01）;纹状体DA及其代谢产物亦较PD模型组显著升高（P〈0.01）。黑质铁染色阳性细胞数量较PD模型组明显减少（P〈0.01）。结论雌激素对PD模型大鼠黑质DA能神经元有明显的保护作用,其作用机制可能与降低铁负载有关。     

Penile lymphoscintigraphy for sentinel node identification

Lymphoscintigraphy for sentinel node (SN) identification has been extensively validated in breast cancer and melanoma. The aim of this study was to evaluate the findings of lymphoscintigraphy for SN identification in carcinoma of the penis. Lymphoscintigraphy was performed in 74 consecutive patients (mean age 62.2 years, range 28-87 years) with clinically lymph node-negative squamous cell carcinoma of the penis (stage T2 or greater). Following local anaesthesia by xylocaine 10% spray, technetium-99m nanocolloid (mean dose 64.8 MBq, range 40-131 MBq) in a volume of 0.3-0.4 ml was injected intradermally around the tumour. Shortly after injection, a 20-min dynamic study was performed with a dual-head gamma camera; subsequently, static anterior and lateral images were obtained at 30 min and 2 h using simultaneous cobalt-57 flood source transmission scanning. ⁵⁷Co-assisted skin marking defined SN location for gamma probe/blue dye-guided biopsy, which was performed the next day. The SN visualization rate was 97% (72/74). Lymphatic drainage was bilateral in 81% of the cases (58/72), exclusively to the left groin in 13% (9/72) and only to the right groin in 6%. Bilateral lymph node drainage was synchronous in 38% (22/58) and asynchronous in 62% (in 18 patients the initial route was the left groin, and in the other 18, the right groin). Visualization before 30 min occurred in 66 patients (93%), in 64 of them (88%) already during the dynamic study. A total of 173 SNs were visualized (85 in the right groin, 88 in the left groin). Pitfalls were caused by inguinal skin contamination during injection (four patients) and intracavernous administration (one patient). At surgery, a total of 161 SNs were identified and removed. Sixteen patients (22%) had a tumour-positive SN and underwent standard regional lymph node dissection subsequently. During follow-up (median 28 months, range 3-74 months), two patients with a negative SN developed lymph node metastases in the mapped basin. It is concluded that penile lymphoscintigraphy is a valid and well-tolerated method for lymphatic mapping and SN identification. Although bilateral early inguinal drainage is the most frequent pattern, late imaging is recommended principally in patients with initial unilateral drainage in order to exclude delayed lymph node filling in the contralateral groin. SN identification may lead to a more accurate staging and avoid extensive lymph node dissection in the majority of patients with penile carcinoma.     

Penile lymphoscintigraphy for sentinel node identification

Lymphoscintigraphy for sentinel node (SN) identification has been extensively validated in breast cancer and melanoma. The aim of this study was to evaluate the findings of lymphoscintigraphy for SN identification in carcinoma of the penis. Lymphoscintigraphy was performed in 74 consecutive patients (mean age 62.2 years, range 28-87 years) with clinically lymph node-negative squamous cell carcinoma of the penis (stage T2 or greater). Following local anaesthesia by xylocaine 10% spray, technetium-99m nanocolloid (mean dose 64.8 MBq, range 40-131 MBq) in a volume of 0.3-0.4 ml was injected intradermally around the tumour. Shortly after injection, a 20-min dynamic study was performed with a dual-head gamma camera; subsequently, static anterior and lateral images were obtained at 30 min and 2 h using simultaneous cobalt-57 flood source transmission scanning. 57Co-assisted skin marking defined SN location for gamma probe/blue dye-guided biopsy, which was performed the next day. The SN visualization rate was 97% (72/74). Lymphatic drainage was bilateral in 81% of the cases (58/72), exclusively to the left groin in 13% (9/72) and only to the right groin in 6%. Bilateral lymph node drainage was synchronous in 38% (22/58) and asynchronous in 62% (in 18 patients the initial route was the left groin, and in the other 18, the right groin). Visualization before 30 min occurred in 66 patients (93%), in 64 of them (88%) already during the dynamic study. A total of 173 SNs were visualized (85 in the right groin, 88 in the left groin). Pitfalls were caused by inguinal skin contamination during injection (four patients) and intracavernous administration (one patient). At surgery, a total of 161 SNs were identified and removed. Sixteen patients (22%) had a tumour-positive SN and underwent standard regional lymph node dissection subsequently. During follow-up (median 28 months, range 3-74 months), two patients with a negative SN developed lymph node metastases in the mapped basin. It is concluded that penile lymphoscintigraphy is a valid and well-tolerated method for lymphatic mapping and SN identification. Although bilateral early inguinal drainage is the most frequent pattern, late imaging is recommended principally in patients with initial unilateral drainage in order to exclude delayed lymph node filling in the contralateral groin. SN identification may lead to a more accurate staging and avoid extensive lymph node dissection in the majority of patients with penile carcinoma.