diff --git a/content/analysis_18f-fdopa.html b/content/analysis_18f-fdopa.html index 6f929b498bd597237e9058700fbc50b500093eda..3127535f200656c09dd7cca4a80d5c3434a22747 100644 --- a/content/analysis_18f-fdopa.html +++ b/content/analysis_18f-fdopa.html @@ -1,7 +1,7 @@ --- title: Analysis of PET measurements of FDOPA author: Vesa Oikonen -updated_at: 2023-11-15 +updated_at: 2023-11-17 created_at: 2009-02-18 tags: - Dopamine @@ -46,7 +46,8 @@ and [<sup>18</sup>F]FPDOPA subsequent build-up of labelled metabolites fluorodopamine (FDA), 6-[<sup>18</sup>F]fluorohomovanillic acid (FHVA), and 6-[<sup>18</sup>F]fluoro-3,4-dihydroxyphenylacetic acid (FDOPAC) -(<a href="https://doi.org/10.1016/S0006-2952(97)00031-2">Barrio et al., 1997</a>). +(<a href="https://doi.org/10.1111/j.1471-4159.1987.tb05629.x">Firnau et al., 1987</a>; +<a href="https://doi.org/10.1016/S0006-2952(97)00031-2">Barrio et al., 1997</a>). FDOPA is also the most used PET tracer for studying hyperinsulinemia and <a href="./tumour_net.html">neuroendocrine tumours</a> (NETs).</p> @@ -164,23 +165,36 @@ the tail of <a href="./organ_pancreas.html">the pancreas</a>.</p> <h3>Gjedde-Patlak graphical analysis with arterial plasma input</h3> <p>Multiple-time graphical analysis for irreversible kinetics -(<a href="./model_mtga.html#patlak">Patlak plot</a>) has frequently been used to analyze brain -[<sup>18</sup>F]FDOPA data, but the labelled metabolites of [<sup>18</sup>F]FDOPA must be accounted -for in the analysis. Plasma data must be corrected for labelled metabolites. -Reference region (cerebellum or occipital cortex) TAC is subtracted from the TAC of -region-of-interest (ROI) or TACs of image pixels. -The radioactivity concentration in reference region consists mainly of -[<sup>18</sup>F]FDOPA and [<sup>18</sup>F]OMFD, and after the subtraction the concentration in +(<a href="./model_mtga.html#patlak">Patlak plot</a>) has frequently been used to assess +the net influx rate constant <em>K<sub>i</sub></em>, representing dopamine synthesis and storage in +the brain. While the synthesized [<sup>18</sup>F]dopamine is stored in the presynaptic vesicles, +some of it is metabolized further into [<sup>18</sup>F]FHVA and [<sup>18</sup>F]FDOPAC, which can +leave the brain, causing underestimation of <em>K<sub>i</sub></em> without observable downward +curvature, even when only 90 min of the data is used +(<a href="https://doi.org/10.1097/01.wcb.0000050041.22945.3e">Sossi et al., 2003</a>). +Brain scans are typically 90 min long, and the time range for Patlak plot line fit is often set to +30-90 min. However, the applied time range for line fit has been varied in +the numerous FDOPA studies applying the Patlak plot, for example, time range 20-70 min was used by +<a href="https://doi.org/10.1176/appi.ajp.162.8.1515">Heinz et al (2005)</a>.</p> + +<p>Peripherally formed labelled metabolites of [<sup>18</sup>F]FDOPA, especially +[<sup>18</sup>F]OMFD, can penetrate BBB, which must be accounted for in the analysis. +The radioactivity concentration in a reference region with little or no AADC activity +(cerebellum or occipital cortex) consists mainly of plasma-derived [<sup>18</sup>F]FDOPA and +[<sup>18</sup>F]OMFD. Reference region TAC is subtracted from the TAC of region-of-interest (ROI) +or TACs of image pixels; after the subtraction the remaining radioactivity concentration in region of interest represents the concentration of [<sup>18</sup>F]FDA and its metabolites, enabling better assessment of AADC activity -(<a href="https://doi.org/10.1002/ana.410260407">Martin et al., 1989</a>).</p> +(<a href="https://doi.org/10.1002/ana.410260407">Martin et al., 1989</a>). +Plasma TAC must be corrected for all labelled metabolites.</p> -<p>In regional analysis the rate constant can be calculated per striatum, -mL plasma)×(striatum×min)<sup>-1</sup>. In this case, striatal ROI is drawn so that it -covers the the whole striatum as visible in the PET image, including any spill-out activity; -the regional radioactivity concentrations (<em>C</em>) and the volumes (<em>V</em>) or areas of -the striatal and reference tissue regions are recorded, and the "specific" striatal radioactivity -(<em>A</em>) is then calculated at each time point as</p> +<p>In regional analysis the Patlak net influx rate constant <em>K<sub>i</sub></em> can be calculated +per striatum, in units (mL plasma)×(striatum×min)<sup>-1</sup>. +In this case, striatal ROI is drawn so that it covers the the whole striatum as visible in +the PET image, including any spill-out activity; the regional radioactivity concentrations +(<em>C</em>) and the volumes (<em>V</em>) or areas of the striatal and reference tissue regions are +recorded, and the "specific" striatal radioactivity (<em>A</em>) is then calculated at each +time point as</p> <a name="striatum"></a> <div class="eqs"> @@ -193,22 +207,31 @@ the striatal and reference tissue regions are recorded, and the "specific" stria <p>(<a href="https://doi.org/10.1002/ana.410260407">Martin et al., 1989</a>). This approach may help to reduce the <a href="./image_pve.html">partial volume effect</a>, and may be clinically more relevant measure -of nigrostriatal function than the striatal average. +of nigrostriatal function than the striatal average; the caudate, putaminal, and thalamic volumes +are negatively correlated with age, and reduced in <a href="./dis_pd.html">Parkinson's disease</a> +(<a href="https://pubmed.ncbi.nlm.nih.gov/8294897/">Lisanby et al., 1993</a>). Usually, though, the subtraction is done simply using regional average TACs, providing also the Patlak net influx rate constant <em>K<sub>i</sub></em> in usual units (mL plasma)×(ml tissue)<sup>-1</sup>×min<sup>-1</sup>. Then the ROIs are usually drawn based on anatomical reference image.</p> -<p>Applied time range for line fit has been varied in the numerous studies applying -the <a href="./model_mtga.html#patlak">Patlak plot</a>. Time range 20-70 min was used by -<a href="https://doi.org/10.1176/appi.ajp.162.8.1515">Heinz et al (2005)</a>.</p> - <h3>Graphical analysis with reference tissue input</h3> -<p>The slope of <a href="./model_mtga.html#patlak_ref">reference tissue MTGA</a> (Patlak plot) is -a function of <em>k<sub>2</sub></em> and <em>k<sub>3</sub></em>:</p> +<p>Cerebellum and occipital cortex are used as reference regions in brain [<sup>18</sup>F]FDOPA +studies. Multiple-time graphical analysis for irreversible kinetics +(<a href="./model_mtga.html#patlak">Patlak plot</a>) can be used with either plasma input function +or with reference tissue input function (<a href="./model_mtga.html#patlak_ref">reference tissue +MTGA</a>). Patlak plot with reference tissue input has been used for example to assess +the rate of loss of nigrostriatal dopaminergic neurons in Parkinson's disease +has been measured using Patlak plot with occipital cortex as reference region +(<a href="https://doi.org/10.1002/mds.1139">Nurmi et al., 2001</a>; +<a href="https://doi.org/10.1002/mds.22484">Brück et al., 2009</a>).</p> + +<p>In case of the reference tissue input, the slope of the Patlak plot +<em>K<sub>i</sub><sup>ref</sup></em> is a function of +<em>k<sub>2</sub></em> and <em>k<sub>3</sub></em>:</p> <a name="kref"></a> <div class="eqs"> @@ -221,11 +244,14 @@ a function of <em>k<sub>2</sub></em> and <em>k<sub>3</sub></em>:</p> <em>K<sub>i</sub><sup>ref</sup></em> results, because the competition affects similarly the reference region and the region of interest (ROI).</p> -<p>Cerebellum and occipital cortex have been used as reference regions. -For example, the rate of loss of nigrostriatal dopaminergic neurons in Parkinson's disease -has been measured using Patlak plot with occipital cortex as reference region -(<a href="https://doi.org/10.1002/mds.1139">Nurmi et al., 2001</a>; -<a href="https://doi.org/10.1002/mds.22484">Brück et al., 2009</a>).</p> +<p>The loss of [<sup>18</sup>F]dopamine metabolites from the striatum causes underestimation of +Patlak plot slope, even more so with reference tissue input than with plasma input +(<a href="https://doi.org/10.1097/01.wcb.0000050041.22945.3e">Sossi et al., 2003</a>). +Presence of [<sup>18</sup>F]OMFD introduces downward curvature in the Patlak plot, causing negative +bias in <em>K<sub>i</sub><sup>ref</sup></em>. The negative bias in amplified with the loss of +dopaminergic neurons, which may explain why reference region input Patlak has been often found to be +the most sensitive marker for <a href="./dis_pd.html">Parkinson's disease</a> +(<a href="https://doi.org/10.1097/01.wcb.0000050041.22945.3e">Sossi et al., 2003</a>).</p> <p><a href="./model_ki_dtp.html#ref">Dual time point imaging</a> can be used to calculate a surrogate parameter to <em>K<sub>i</sub><sup>ref</sup></em>